miR-146a和MIF基因多态性与胃癌遗传易感性研究
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摘要
胃癌是最常见的消化道恶性肿瘤之一。虽然自20世纪30年代以来,胃癌的发病率在世界范围内呈下降趋势,但仍然位居肿瘤致死原因的第二位。中国属于胃癌高发区,胃癌仍然是威胁我国居民健康的重要疾病之一。胃癌的发生是多步骤、多因素的,是环境因素和遗传因素共同作用的结果。已证实其发病风险和多种基因的多态性相关,这些基因编码的信号分子包括miRNAs(microRNAs)、免疫球蛋白超家族成员、代谢酶、以及参与炎症反应、DNA修复、氧化损伤的多种信号分子等。研究者以基因遗传变异为切入点,研究其与胃癌遗传易感性的关系。鉴于胃癌多病因、涉及不同信号通路的特点,本研究着重对编码微RNAs的基因变异和炎症反应信号分子的基因变异与胃癌的遗传易感性进行了深入的研究。
已有研究证实,miR-146a(microRNA-146a)和巨噬细胞移动抑制因子(Macrophage migration inhibitory factor, MIF)参与癌症发生发展。而编码这些蛋白的基因的单核苷酸多态性如Pre-miR-146a C/G、MIF-173 G/C也与基因表达水平和(或)蛋白功能密切相关。目前尚无研究关注这些基因单核苷酸多态性与胃癌遗传易感性的关系,因此,本研究采用病例对照设计,用单因素和多因素的统计分析方法,研究了Pre-miR-146a C/G和MIF-173 G/C基因多态性与胃癌遗传易感性的关系。
本研究可发现与胃癌发病相关的基因型,为胃癌高危人群或易感个体的筛查提供诊断指标;可从遗传学角度进一步阐明胃癌的发病机制,为胃癌的预防和治疗提供理论依据。
第一部分:Pre-miR-146a C/G基因多态性与胃癌遗传易感性
为研究Pre-miR-146a C/G基因多态性和胃癌患病风险的相关性,我们进行了一项以医院为基础的病例对照研究。研究对象为304位胃癌病人和304位年龄及性别配对的对照受试者,基因型是通过PCR-RFLP方法测定。病例组和对照组基因型分布存在统计学差异(P=0.037)。相对纯合子CC基因型携带者,变异基因型(CG+GG)携带者患胃癌的风险增加了58%比值比[校正比值比(Odds Ratio,OR)为1.58,95%可信区间(Confidence Interval, CI)为1.12-2.22]。分层分析结果显示变异基因型增加的胃癌风险在低年龄组(年龄≤58)、男性和非吸烟者有显著意义(校正OR分别是1.76、1.53和1.55;95%CI分别是1.08-2.87,1.04-2.27和1.06-2.28)。进一步对肿瘤分化程度、浸润深度、发病部位和淋巴结转移等临床病理学特征与变异基因型的相关性进行分层分析,结果显示无统计学差异。研究结果表明Pre-miR-146a C/G多态性和胃癌发病风险相关。
第二部分:巨噬细胞移动抑制因子-173G/C基因多态性与胃癌遗传易感性
MIF是T细胞分化的细胞因子,能抑制巨噬细胞迁移,在炎症反应、酶和激素的活化以及肿瘤的发生中发挥重要作用。MIF基因位于染色体22q11.2位点,其-173G/C(rs755622)单核苷酸多态性与多种疾病的易感性密切相关。为研究MIF-173G/C多态性和胃癌风险的相关性,我们进行一项以医院为基础的病例对照研究。研究对象为283个胃癌病例和283个年龄及性别匹配的对照,基因型是通过PCR-RFLP方法测定。病例组和对照组基因型分布存在统计学差异(P=0.008)。病例组变异C等位基因频率高于对照组(P=0.015)。相对野生GG基因型携带者,变异纯合子CC基因型携带者患胃癌的风险增加3.49倍(校正OR=3.49, 95%CI=1.53-7.97)。进一步分层分析显示变异基因型(GC+CC)增加的胃癌风险在男性组有显著意义(校正OR=1.52, 95%CI=1.03-2.25)。进一步对胃癌病人的临床病理特征分层分析显示,变异基因型(GC+CC)与肿瘤浸润深度正相关。研究结果表明MIF-173G/C多态性是胃癌的一个遗传易感因素。
通过对以上涉及不同通路信号分子基因变异与胃癌风险相关性的研究,并在考虑了性别、年龄、吸烟状态、居住环境、高血压和糖尿病等因素后进行的多因素分析结果,进一步佐证了胃癌的发生是多因素和多阶段逐步演变的过程,有助于在分子水平加深对胃癌病因和发病机制的认识。研究结果为制定胃癌高危人群的筛选提供了筛选指标,对胃癌的个性化预防、治疗措施提供了重要的理论依据。
Gastric cancer is a major cause of morbidity and mortality among malignant tumor of digestive tract. Although the incidence of gastric cancer has decreased since the 1930s, it remains the second most fatal malignancy in the world. Gastric cancer is a major public health issue in China where about half of the worldwide gastric cancer cases occur. It is a complex, multistep and multifactorial process, and is thought to result from an interaction between genetic backgrounds and environmental factors. Epidemiological studies show that the risk of gastric cancer was influenced by polymorphisms of many genes including microRNAs, immunoglobulin superfamily members, metabolic enzymes, other molecules involved in inflammatory response, DNA repair, oxidative damage, and et al. Our group explored the molecular markers with potential to predict occurrence and progression of gastric cancer, based on the hypothesis that there might be a similar genetic background that makes some individuals more susceptible to gastric cancer and liable to metastases in cancer progression. In the present study, we are particularly focusing on the single nucleotide polymorphisms (SNPs) of genes encoding microRNAs and immunoglobulin superfamily members.
Recently, microRNA-146a (miRNA-146a) and Macrophage migration inhibitor factor (MIF) have been linked to tumorigenesis. SNPs of these genes including Pre-miR-146a C/G and MIF-173G/C have been confirmed to be associated with the expression of the genes and (or) the function of the proteins.
However, to our knowledge, there is no study concerning association between these polymorphisms and susceptibility to gastric cancer. Thus, we conducted a hospital-based, case-control study to assess the association between the risk of gastric cancer and the Pre-miR-146a C/G and MIF-173G/C polymorphism by univariate and multivariate analysis.
It is important to find the polymorphisms which could be used as the marker for genetic susceptibility to gastric cancer. Identification of genetic factors that are responsible for susceptibility to gastric cancer is indispensable for establishing novel and efficient ways of preventing the disease.
PartⅠ: A Study on the Association between Pre-miR-146a C/G Polymorphism and Susceptibility to Gastric Cancer
To investigate the association between Pre-miR-146a C/G polymorphism and gastric cancer risk, we conducted a hospital-based case-control study of 304 gastric cancer cases and 304 controls matched on age and gender. The genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). We found that the genotype frequencies were significantly different (P=0.037) between cases and controls. Compared with the CC homozygotes, the variant genotypes (CG + GG) were associated with a 58% increased risk of gastric cancer (adjusted OR=1.58, 95% CI=1.12-2.22). Further stratification analyses indicated that the increased risk was especially noteworthy in young subjects (age≤58) (adjusted OR=1.76, 95% CI=1.08-2.87), males (adjusted OR=1.53, 95% CI=1.04-2.27) and non-smokers (adjusted OR=1.55, 95% CI=1.06-2.28). We also evaluated the correlations of the variant genotypes with clinicopathologic features of gastric cancer, including tumor differentiation, depth of tumor infiltration, lymph node status and tumor location. However, no statistically significant association was observed. Our results suggest that the Pre-miR-146a C/G polymorphism may be associated with increased risk of gastric cancer.
PartⅡ: A Study on the Association between MIF-173G/C Polymorphism and Susceptibility to Gastric Cancer
Macrophage migration inhibitory factor (MIF) is a T cell-derived cytokine that inhibits the migration of macrophages and play an important pathogenetic role in proinflammatory, enzymatic and hormonal activities. The MIF gene maps to chromosome 22q11.2, and its -173G/C (rs755622) polymorphism has been shown to influence susceptibility to several diseases. To investigate the association between MIF-173G/C polymorphism and gastric cancer risk, we conducted a hospital-based case-control study of 283 gastric cancer cases and 283 controls matched on age and gender. The genotype and allele frequencies were significantly different (P=0.008 and 0.015, respectively) between cases and controls. Further analysis showed that the variant CC genotype had a 3.49-fold increased risk of gastric cancer when compared with GG genotype (adjusted OR=3.49, 95% CI=1.53-7.97). The elevated gastric cancer risk associated with the variant genotypes ( GC + CC) was observed only in male subjects (adjusted OR=1.52, 95% CI=1.03-2.25), but not in females. Further analyses revealed that the variant genotypes (GC+CC) were associated with depth of tumor infiltration. These findings suggest that the MIF-173G/C polymorphism is a genetic predisposing factor for gastric cancer.
In summary, we have suggested the polymorphisms of genes involved in different pathogenic pathways in gastric carcinogenesis. Further investigations of the combined effects of polymorphisms within these genes and risk factors may help to clarify the influence of genetic variation in the carcinogenic process.
已有研究证实,miR-146a(microRNA-146a)和巨噬细胞移动抑制因子(Macrophage migration inhibitory factor, MIF)参与癌症发生发展。而编码这些蛋白的基因的单核苷酸多态性如Pre-miR-146a C/G、MIF-173 G/C也与基因表达水平和(或)蛋白功能密切相关。目前尚无研究关注这些基因单核苷酸多态性与胃癌遗传易感性的关系,因此,本研究采用病例对照设计,用单因素和多因素的统计分析方法,研究了Pre-miR-146a C/G和MIF-173 G/C基因多态性与胃癌遗传易感性的关系。
本研究可发现与胃癌发病相关的基因型,为胃癌高危人群或易感个体的筛查提供诊断指标;可从遗传学角度进一步阐明胃癌的发病机制,为胃癌的预防和治疗提供理论依据。
第一部分:Pre-miR-146a C/G基因多态性与胃癌遗传易感性
为研究Pre-miR-146a C/G基因多态性和胃癌患病风险的相关性,我们进行了一项以医院为基础的病例对照研究。研究对象为304位胃癌病人和304位年龄及性别配对的对照受试者,基因型是通过PCR-RFLP方法测定。病例组和对照组基因型分布存在统计学差异(P=0.037)。相对纯合子CC基因型携带者,变异基因型(CG+GG)携带者患胃癌的风险增加了58%比值比[校正比值比(Odds Ratio,OR)为1.58,95%可信区间(Confidence Interval, CI)为1.12-2.22]。分层分析结果显示变异基因型增加的胃癌风险在低年龄组(年龄≤58)、男性和非吸烟者有显著意义(校正OR分别是1.76、1.53和1.55;95%CI分别是1.08-2.87,1.04-2.27和1.06-2.28)。进一步对肿瘤分化程度、浸润深度、发病部位和淋巴结转移等临床病理学特征与变异基因型的相关性进行分层分析,结果显示无统计学差异。研究结果表明Pre-miR-146a C/G多态性和胃癌发病风险相关。
第二部分:巨噬细胞移动抑制因子-173G/C基因多态性与胃癌遗传易感性
MIF是T细胞分化的细胞因子,能抑制巨噬细胞迁移,在炎症反应、酶和激素的活化以及肿瘤的发生中发挥重要作用。MIF基因位于染色体22q11.2位点,其-173G/C(rs755622)单核苷酸多态性与多种疾病的易感性密切相关。为研究MIF-173G/C多态性和胃癌风险的相关性,我们进行一项以医院为基础的病例对照研究。研究对象为283个胃癌病例和283个年龄及性别匹配的对照,基因型是通过PCR-RFLP方法测定。病例组和对照组基因型分布存在统计学差异(P=0.008)。病例组变异C等位基因频率高于对照组(P=0.015)。相对野生GG基因型携带者,变异纯合子CC基因型携带者患胃癌的风险增加3.49倍(校正OR=3.49, 95%CI=1.53-7.97)。进一步分层分析显示变异基因型(GC+CC)增加的胃癌风险在男性组有显著意义(校正OR=1.52, 95%CI=1.03-2.25)。进一步对胃癌病人的临床病理特征分层分析显示,变异基因型(GC+CC)与肿瘤浸润深度正相关。研究结果表明MIF-173G/C多态性是胃癌的一个遗传易感因素。
通过对以上涉及不同通路信号分子基因变异与胃癌风险相关性的研究,并在考虑了性别、年龄、吸烟状态、居住环境、高血压和糖尿病等因素后进行的多因素分析结果,进一步佐证了胃癌的发生是多因素和多阶段逐步演变的过程,有助于在分子水平加深对胃癌病因和发病机制的认识。研究结果为制定胃癌高危人群的筛选提供了筛选指标,对胃癌的个性化预防、治疗措施提供了重要的理论依据。
Gastric cancer is a major cause of morbidity and mortality among malignant tumor of digestive tract. Although the incidence of gastric cancer has decreased since the 1930s, it remains the second most fatal malignancy in the world. Gastric cancer is a major public health issue in China where about half of the worldwide gastric cancer cases occur. It is a complex, multistep and multifactorial process, and is thought to result from an interaction between genetic backgrounds and environmental factors. Epidemiological studies show that the risk of gastric cancer was influenced by polymorphisms of many genes including microRNAs, immunoglobulin superfamily members, metabolic enzymes, other molecules involved in inflammatory response, DNA repair, oxidative damage, and et al. Our group explored the molecular markers with potential to predict occurrence and progression of gastric cancer, based on the hypothesis that there might be a similar genetic background that makes some individuals more susceptible to gastric cancer and liable to metastases in cancer progression. In the present study, we are particularly focusing on the single nucleotide polymorphisms (SNPs) of genes encoding microRNAs and immunoglobulin superfamily members.
Recently, microRNA-146a (miRNA-146a) and Macrophage migration inhibitor factor (MIF) have been linked to tumorigenesis. SNPs of these genes including Pre-miR-146a C/G and MIF-173G/C have been confirmed to be associated with the expression of the genes and (or) the function of the proteins.
However, to our knowledge, there is no study concerning association between these polymorphisms and susceptibility to gastric cancer. Thus, we conducted a hospital-based, case-control study to assess the association between the risk of gastric cancer and the Pre-miR-146a C/G and MIF-173G/C polymorphism by univariate and multivariate analysis.
It is important to find the polymorphisms which could be used as the marker for genetic susceptibility to gastric cancer. Identification of genetic factors that are responsible for susceptibility to gastric cancer is indispensable for establishing novel and efficient ways of preventing the disease.
PartⅠ: A Study on the Association between Pre-miR-146a C/G Polymorphism and Susceptibility to Gastric Cancer
To investigate the association between Pre-miR-146a C/G polymorphism and gastric cancer risk, we conducted a hospital-based case-control study of 304 gastric cancer cases and 304 controls matched on age and gender. The genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). We found that the genotype frequencies were significantly different (P=0.037) between cases and controls. Compared with the CC homozygotes, the variant genotypes (CG + GG) were associated with a 58% increased risk of gastric cancer (adjusted OR=1.58, 95% CI=1.12-2.22). Further stratification analyses indicated that the increased risk was especially noteworthy in young subjects (age≤58) (adjusted OR=1.76, 95% CI=1.08-2.87), males (adjusted OR=1.53, 95% CI=1.04-2.27) and non-smokers (adjusted OR=1.55, 95% CI=1.06-2.28). We also evaluated the correlations of the variant genotypes with clinicopathologic features of gastric cancer, including tumor differentiation, depth of tumor infiltration, lymph node status and tumor location. However, no statistically significant association was observed. Our results suggest that the Pre-miR-146a C/G polymorphism may be associated with increased risk of gastric cancer.
PartⅡ: A Study on the Association between MIF-173G/C Polymorphism and Susceptibility to Gastric Cancer
Macrophage migration inhibitory factor (MIF) is a T cell-derived cytokine that inhibits the migration of macrophages and play an important pathogenetic role in proinflammatory, enzymatic and hormonal activities. The MIF gene maps to chromosome 22q11.2, and its -173G/C (rs755622) polymorphism has been shown to influence susceptibility to several diseases. To investigate the association between MIF-173G/C polymorphism and gastric cancer risk, we conducted a hospital-based case-control study of 283 gastric cancer cases and 283 controls matched on age and gender. The genotype and allele frequencies were significantly different (P=0.008 and 0.015, respectively) between cases and controls. Further analysis showed that the variant CC genotype had a 3.49-fold increased risk of gastric cancer when compared with GG genotype (adjusted OR=3.49, 95% CI=1.53-7.97). The elevated gastric cancer risk associated with the variant genotypes ( GC + CC) was observed only in male subjects (adjusted OR=1.52, 95% CI=1.03-2.25), but not in females. Further analyses revealed that the variant genotypes (GC+CC) were associated with depth of tumor infiltration. These findings suggest that the MIF-173G/C polymorphism is a genetic predisposing factor for gastric cancer.
In summary, we have suggested the polymorphisms of genes involved in different pathogenic pathways in gastric carcinogenesis. Further investigations of the combined effects of polymorphisms within these genes and risk factors may help to clarify the influence of genetic variation in the carcinogenic process.
引文
[1] Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin,2005,55(2):74-108.
[2] Kelley JR, Duggan JM. Gastric cancer epidemiology and risk factors. J Clin Epidemiol,2003,56(1):1-9.
[3] Wu MS, Chen CJ, Lin JT. Host-environment interactions: their impact on progression from gastric inflammation to carcinogenesis and on development of new approaches to prevent and treat gastric cancer. Cancer Epidemiol Biomarkers Prev,2005,14(8):1878–82.
[4] Zhu H, Yang L, Zhou B, Yu R, Tang N, Wang B. Myeloperoxidase G-463A polymorphism and the risk of gastric cancer: a case-control study. Carcinogenesis, 2006,27(12):2491-2496.
[5] Yang L, Zhu H, Zhou B, Gu H, Yan H, Tang N, Dong H, Sun Q, Cong R, Chen G, Wang B. The Association Between the Survivin C-31G Polymorphism and Gastric Cancer Risk in a Chinese Population. Dig Dis Sci,2009;54(5):1021-1028.
[6] Gu H, Yang L, Sun Q, Zhou B, Tang N, Cong R, Zeng Y, Wang B. Gly82Ser polymorphism of the receptor for advanced glycation end products is associated with an increased risk of gastric cancer in a Chinese population. Clin Cancer Res,2008;14(11):3627-32.
[7] Yang L, Gu HJ, Zhu HJ, et al. Tissue inhibitor of metalloproteinase-2 G-418C polymorphism is associated with an increased risk of gastric cancer in a Chinese population. Eur J Surg Oncol 2008;34(6):636-641.
[8] Gu H, Yang L, Tang N, Zhou B, Zhu H, Sun Q, Cong R, Wang B. Association of endothelin-converting enzyme-1b C-338A polymorphism with gastric cancer risk: a case-control study.Eur J Cancer,2008;44(9):1253-1258.
[1] Ambros V. microRNAs: tiny regulators with great potential. Cell, 2001; 107: 823-826.
[2] Punj V, Matta H, Schamus S, Tamewitz A, Anyang B, Chaudhary PM. Kaposi's sarcoma-associated herpesvirus-encoded viral FLICE inhibitory protein (vFLIP) K13 suppresses CXCR4 expression by upregulating miR-146a. Oncogene,2010,29(12):1835-1844.
[3] Bhaumik D, Scott GK, Schokrpur S, Patil CK, Campisi J, Benz CC. Expression of microRNA-146 suppresses NF-kappaB activity with reduction of metastatic potential in breast cancer cells. Oncogene,2008,27(42):5643-5647.
[4] Pacifico F, Crescenzi E, Mellone S, Iannetti A, Porrino N, Liguoro D, Moscato F, Grieco M, Formisano S, Leonardi A. Nuclear Factor-{kappa}B Contributes to Anaplastic Thyroid Carcinomas through Up-Regulation of miR-146a. J Clin Endocrinol Metab,2010,95(3):1421-1430.
[5] Motsch N, Pfuh1 T, Mrazek J, Barth S, Grasser FA. Epstein-Barr virus-encoded latent membrane protein 1 (LMP1) induces the expression of the cellular microRNA miR-146a. RNA Biol,2007,4(3):131-137.
[6] Labbaye C, Spinello I, Quaranta MT, Pelosi E, Pasquini L, Petrucci E, Biffoni M, Nuzzolo ER, Billi M, FoàR, Brunetti E, Grignani F, Testa U, Peschle C. A three-step pathway comprising PLZF/miR-146a/CXCR controls megakaryopoiesis. Nat Cell Biol,2008,10(7):788-801.
[7] Hurst DR, Edmonds MD, Scott GK, Benz CC, Vaidya KS, Welch DR. Breast cancer metastasis suppressor 1 up-regulates miR-146, which suppresses breast cancer metastasis. Cancer Res,2009,69(4):1279-1283.
[8] Kuang W, Tan J, Duan Y, Duan J, Wang W, Jin F, Jin Z, Yuan X, Liu Y. Cyclic stretch induced miR-146a upregulation delays C2C12 myogenic differentiationthrough inhibition of Numb. Biochem Biophys Res Commun,2009,378(2): 259-263.
[9] Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt RL, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, Harris CC, Croce CM. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A,2006,103(7):2257-2261.
[10] Lin SL, Chiang A, Chang D, Ying SY. Loss of mir-146a function in hormone-refractory prostate cancer. RNA,2008,14(3):417-424.
[11] Wang X, Tang S, Le SY, Lu R, Rader JS, Meyers C, Zheng ZM. Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth. PLoS One,2008,3(7):e2557.
[12] Yang W, Chendrimada TP, Wang Q, Higuchi M, Seeburg PH, Shiekhattar R, Nishikura K. Modulation of microRNA processing and expression through RNA editing by ADAR deaminases. Nat Struct Mol Biol, 2006, 13(1):13-21
[13] Iwai N , Naraba H. Polymorphisms in human pre-miRNA. Biochem Biophys Res Commun,2005,331(4):1439-1444.
[14] Jazdzewski K, Murray EL, Franssila K, Jarzab B, Schoenberg DR, de la Chapelle A. Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci U S A,2008,105(20):7269-7274.
[15] Xu T, Zhu Y, Wei QK, et al. A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma. Carcinogenesis,2008,29(11):2126-2131.
[16] Xu B, Feng NH, Li PC, Tao J, Wu D, Zhang ZD, Tong N, Wang JF, Song NH, Zhang W, Hua LX, Wu HF. A functional polymorphism in Pre-miR-146a gene isassociated with prostate cancer risk and mature miR-146a expression in vivo. Prostate,2010,70(5):467-472.
[17] Shen J, Ambrosone CB, DiCioccio RA, Odunsi K, Lele SB, Zhao H. A functional polymorphism in the miR-146a gene and age of familial breast/ovarian cancer diagnosis. Carcinogenesis,2008,29(10):1963-1966.
[18] Hu Z, Liang J, Wang Z, Tian T, Zhou X, Chen J, Miao R, Wang Y, Wang X, Shen H. Common genetic variants in pre-microRNAs were associated with increased risk of breast cancer in Chinese women. Hum Mutat,2009,30(1):79-84.
[19] Sobin LH, Wittekind CH. editors. TNM classification of malignant tumors. 5th ed. New York: Wiley & Sons, Inc,1997.59–62.
[20] Wang L, Wei D, Huang S, Peng Z, Le X, Wu TT, Yao J, Ajani J, Xie K. Transcription factor Sp1 expression is a significant predictor of survival in human gastric cancer. Clin Cancer Res, 2003, 9(17):6371-6380.
[21] Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, Iorio MV, Visone R, Sever NI, Fabbri M, Iuliano R, Palumbo T, Pichiorri F, Roldo C, Garzon R, Sevignani C, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med, 2005, 353(17):1793-1801.
[22] Raveche ES, Salerno E, Scaglione BJ, Manohar V, Abbasi F, Lin YC, Fredrickson T, Landgraf P, Ramachandra S, Huppi K, Toro JR, Zenger VE, Metcalf RA, Marti GE. Abnormal microRNA-16 locus with synteny to human 13q14 linked to CLL in NZB mice. Blood, 2007, 109(12):5079-5086.
[23] Zeng Y, Yi R, Cullen BR. Recognition and cleavage of primary microRNA precursors by the nuclear processing enzyme Drosha. EMBO J, 2005, 24(1):138-148.
[24] Zeng Y, Cullen BR. Sequence requirements for micro RNA processing and function in human cells. RNA, 2003, 9(1):112-123.
[25] Karin M. NF-kappaB as a critical link between inflammation and cancer. Cold Spring Harbor Perspect Biol, 2009,1(5):a000141.
[26] Naugler WE, Karin M. NF-kappaB and cancer-identifying targets and mechanisms. Curr Opin Genet Dev, 2008,18(1):19-26.
[27] Nahid MA, Pauley KM, Satoh M, Chan EK. miR-146a is critical for endotoxin-induced tolerance: IMPLICATION IN INNATE IMMUNITY. J Biol Chem, 2009, 284(50):34590-34599.
[28] Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A, 2006,103(33):12481-12486.
[29] Cameron JE, Yin Q, Fewell C, Lacey M, McBride J, Wang X, Lin Z, Schaefer BC, Flemington EK. Epstein-Barr virus latent membrane protein 1 induces cellular MicroRNA miR-146a, a modulator of lymphocyte signaling pathways. J Virol, 2008,82(4): 1946-1958.
[30] Nakasa T, Miyaki S, Okubo A, Hashimoto M, Nishida K, Ochi M, Asahara H. Expression of microRNA-146 in rheumatoid arthritis synovial tissue. Arthritis Rheum, 2008, 58(5): 1284-1292.
[31] Stanczyk J, Pedrioli DM, Brentano F, Sanchez-Pernaute O, Kolling C, Gay RE, Detmar M, Gay S, Kyburz D. Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis. Arthritis Rheum, 2008, 58(4): 1001-1009.
[32] Ruan K, Fang X, Ouyang G. MicroRNAs: novel regulators in the hallmarks of human cancer. Cancer Lett, 2009, 285(2): 116-126.
[33] Rehmsmeier M, Steffen P, Hochsmann M, Giegerich R. Fast and effectiveprediction of microRNA/target duplexes. RNA, 2004, 10(10): 1507-1517.
[34] Jazdzewski K, Murray EL , Murray KF , et al . Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci U S A,2008,105(20):7269-7274.
[35] Zhu H, Yang L, Zhou B, Yu R, Tang N, Wang B. Myeloperoxidase G-463A polymorphism and the risk of gastric cancer: a case-control study. Carcinogenesis,2006, 27(12):2491-2496.
[36] Parkin DM. International variation. Oncogene, 2004,23(38):6329-40.
[37] Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin,2005,55(2):74-108.
[1] Leng L, Bucala R. Macrophage migration inhibitory factor. Crit Care Med, 2005, 33(12 Suppl): S475-S477.
[2] Bach JP, Rinn B, Meyer B, Dodel R, Bacher M. Role of MIF in inflammation and tumorigenesis. Oncology,2008, 75(3-4):127-133.
[3] Bucala R, Donnelly SC. Macrophage migration inhibitory factor: a probable link between inflammation and cancer. Immunity, 2007, 26(3): 281-285.
[4] Calandra T, Roger T. Macrophage migration inhibitory factor: a regulator of innate immunity. Nat Rev Immunol, 2003;3(10): 791-800.
[5] De Jong YP, Abadia-Molina AC, Satoskar AR, Clarke K, Rietdijk ST, Faubion WA, Mizoguchi E, Metz CN, Alsahli M, ten Hove T, Keates AC, Lubetsky JB, Farrell RJ, Michetti P, van Deventer SJ, Lolis E, David JR, Bhan AK, Terhorst C. Development of chronic colitis is dependent on the cytokine MIF. Nat Immunol, 2001,2(11):1061–1066.
[6] Shimizu T, Nishihira J, Mizue Y, Nakamura H, Abe R, Watanabe H, Ohkawara A, Shimizu H. High macrophage migration inhibitory factor (MIF) serum levels associated with extended psoriasis. J Invest Dermatol, 2001,116(6):989–990.
[7] Leech M, Metz C, Hall P, Hutchinson P, Gianis K, Smith M, Weedon H, Holdsworth SR, Bucala R, Morand EF. Macrophage migration inhibitory factor in rheumatoid arthritis: evidence of proinflammatory function and regulation by glucocorticoids. Arthritis Rheum, 1999,42(8):1601–1608.
[8] Repp AC, Mayhew ES, Apte S, Niederkorn JY. Human uveal melanoma cells produce macrophage migration-inhibitory factor to prevent lysis by NK cells. J Immunol, 2000;165(2):710–715.
[9] Akbar SM, Abe M, Murakami H, Tanimoto K, Kumagi T, Yamashita Y, Michitaka K, Horiike N, Onji M. Macrophage migration inhibitory factor inhepatocellular carcinoma and liver cirrhosis: relevance to pathogenesis. Cancer Lett, 2001;171(2):125–132.
[10] He XX, Yang J, Ding YW, Liu W, Shen QY, Xia HH. Increased epithelial and serum expression of m acrophage migration inhibitory factor (MIF) in gastric cancer:potential role of M IF in gastric carcinogenesis.Gut,2006,55(6):797-802.
[11] Shun CT, Lin JT, Huang SP, Lin MT, Wu MS. Expression of macrophage migration inhibitory factor is associated with enhanced angiogenesis and advanced stage in gastric carcinomas.World J Gastroenterol,2005,11(24):3767-3771.
[12] Donn R, Alourfi Z, De Benedetti F, Meazza C, Zeggini E, Lunt M, Stevens A, Shelley E, Lamb R, Ollier WE, Thomson W, Ray D; British Paediatric Rheumatology Study Group. Mutation screening of the macrophage migration inhibitory factor gene: positive association of a functional polymorphism of macrophage migration inhibitory factor with juvenile idiopathic arthritis.Arthritis Rheum, 2002: 46(9): 2402–2409.
[13] Baugh JA, Chitnis S, Donnelly SC, Monteiro J, Lin X, Plant BJ, Wolfe F, Gregersen PK, Bucala R. Afunctional promoter polymorphism in the macrophage migration inhibitory factor (MIF) gene associated with disease severity in rheumatoid arthritis. Genes Immun, 2002, 3(3): 170–176.
[14] Sanchez E, Gomez LM, Lopez-Nevot MA, Sabio JM, Ortego-Centeno N, de Ramón E, Anaya JM, González-Escribano MF, Koeleman BP, Martín J. Evidence of association of macrophage migration inhibitory factor gene polymorphisms with systemic lupus erythematosus. Genes Immun, 2006, 7(5): 433–436.
[15] Awandare GA, Ouma C, Keller CC, Were T, Otieno R, Ouma Y, Davenport GC, Hittner JB, Ong'echa JM, Ferrell R, Perkins DJ. A macrophage migrationinhibitory factor promoter polymorphism is associated with high-density parasitemia in children with malaria. Genes Immun, 2006, 7(7): 568-575.
[16] Donn R, Alourfi Z, De Benedetti F, Meazza C, Zeggini E, Lunt M, Stevens A, Shelley E, Lamb R, Ollier WE, Thomson W, Ray D; British Paediatric Rheumatology Study Group. Mutation screening of the macrophage migration inhibitory factor gene. Arthritis Rheum, 2002, 46(9): 2402 - 2409.
[17] Gómez LM, Sánchez E, Ruiz-Narvaez EA, López-Nevot MA, Anaya JM, Martín J. Macrophage migration inhibitory factor gene influences the risk of developing tuberculosis in northwestern Colombian population. Tissue Antigens, 2007,70(1):28-33.
[18] Ding GX, Zhou SQ, Xu Z, Feng NH, Song NH, Wang XJ, Yang J, Zhang W, Wu HF, Hua LX. The Association Between MIF-173 G>C Polymorphism and Prostate Cancer in Southern Chinese. Journal of Surgical Oncology, 2009,100(2):106–110.
[19] Xue Y, Xu H, Rong L, Lu Q, Li J, Tong N, Wang M, Zhang Z, Fang Y. The MIF -173G/C polymorphism and risk of childhood acute lymphoblastic leukemia in a Chinese population. Leuk Res. 2010 May 4.
[20] de la Fontaine L, Schwarz MJ, Riedel M, Dehning S, Douhet A, Spellmann I, Kleindienst N, Zill P, Plischke H, Gruber R, Müller N. Investigating disease susceptibility and the negative correlation of schizophrenia and rheumatoid arthritis focusing on MIF and CD14 gene polymorphisms. Psychiatry Res, 2006,30;144(1):39-47
[21] Donn RP, Shelley E, Ollier WE, Thomson W; British Paediatric Rheumatology Study Group. A novel 5'-flanking region polymorphism of macrophage migration inhibitory factor is associated with systemic-onset juvenile idiopathic arthritis. Arthritis Rheum. 2001,44(8):1782-1785.
[22] Sun HW,Bernhagen J,Bucala R,Lolis E. Crystal structure at 2.6-A resolution of human macrophage migration inhibitory factor. Proc NatlAcad Sci USA, 1996,93(11):5191-5196.
[23] Baugh J A, Bucala R. Macrophage migration inhibitory factor. J CritCare Med,2002,30(1 Supp):27-35.
[24] Bernhagen J, Calandra T, Mitchell RA, Martin SB, Tracey KJ, Voelter W, Manogue KR, Cerami A, Bucala R. Nature, 1993, 365(6448):756-759.
[25] Bucala R. MIF, a previously unrecognized pituitary hormone and macrophage cytokine,is a pivotal mediator in endotoxie shock. Circulation Shock, 1994, 44(1):35-39.
[26] Calandra T, Bernhagen J, Mitchell RA, Bucala R. The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor. Exp Med, 1994,179(6):1895-1902.
[27] Bacher M, Metz CN, Calandra T, Mayer K, Chesney J, Lohoff M, Gemsa D, Donnelly T, Bucala R. An essential regulatory role for macrophage migration inhibitory factor in T-cell activation. Proc Natl Acad Sci U S A, 1996;93(15):7849-7854.
[28] Calandra T, Bernhagen J, Metz CN, Spiegel LA, Bacher M, Donnelly T, Cerami A, Bucala R. MIF as a glucocorticoid-induced modulator of cytokine production. Nature, 1995;377(6544):68-71.
[29] Xia HH, Lam SK, Huang XR, Wong WM, Leung SY, Yuen ST, Lan HY, Wong BC. Helicobacter pylori infection is associated with increased expression of macrophage migratory inhibitory factor--by epithelial cells, T cells, and macrophages--in gastric mucosa. J Infect Dis, 2004; 190(2): 293-302.
[30] Mitchell RA. Mechanisms and effectors of MIF-dependent promotion of tumourigenesis. Cell Signal, 2004; 16(1): 13-19.
[31] Lue H, Kapurniotu A, Fingerle-Rowson G, Roger T, Len L, Thiele M, Calandra T, Bucala R, Bernhagen J. Rapid and transient activation of the ERK MAPK signalling pathway by macrophage migration inhibitory factor (MIF) and dependence on JAB1/CSN5 and Src kinase activity. Cell Signal, 2006, 18(5):688-703.
[32] Lue H, Thiele M, Franz J, Dahl E, Speckgens S, Leng L, Fingerle-Rowson G, Bucala R, Lüscher B, Bernhagen J. Macrophage migration inhibitory factor (MIF) promotes cell survival by activation of the Akt pathway and role for CSN5/JAB1 in the control of autocrine MIF activity. Oncogene, 2007, 26(35): 5046-5059.
[33] Petrenko O, Moll UM. Macrophage migration inhibitory factor MIF interferes with the Rb-E2F pathway. Mol Cell, 2005, 17(2): 225-236.
[34] Li GQ, Xie J, Lei XY, Zhang L. Macrophage migration inhibitory factor regulates proliferation of gastric cancer cells via the PI3K/Akt pathway. World J Gastroenterol, 2009,15(44):5541-5548.
[35] Yu BH, Zhou XY. Advances on PI3K/Akt/mTOR signalling pathway in malignancies. Zhonghua Binglixue Zazhi, 2005, 34(10):674-676.
[36] Tokunaga E, Oki E, Egashira A, Sadanaga N, Morita M, Kakeji Y, Maehara Y. Deregulation of the Akt pathway in human cancer. Curr Cancer Drug Targets, 2008, 8(1): 27-36.
[37] Michl P, Downward J. Mechanisms of disease: PI3K/AKT signaling in gastrointestinal cancers. Z Gastroenterol, 2005,43(10): 1133-1139.
[38] Metz CN , Bucala R. Role of macrophage migration inhibitory factor in the regulation of the immune response. Adv Immunol, 1997, 66 (3):197-223.
[39] Miechell RA, Bucala R. Tumor growth promoting properties of macrophage migration inhibitory factor (MIF). Semin Cancer Biol , 2000, 10 (5): 359-366.
[40] Hudson JD, Shoaibi MA , Maestro R, Carnero A, Hannon GJ, Beach DH. Aproinflammatory cytokine inhibits p53 tumor suppressor activity. J Exp Med, 1999, 190 (10): 1375-1382.
[1] Gangaraju VK, Lin H. MicroRNAs: key regulators of stem cells. Nat Rev Mol Cell Biol, 2009,10(2):116–25.
[2] Asli NS, Pitulescu ME, Kessel M. MicroRNAs in organogenesis and disease. Curr Mol Med, 2008,8(8):698–710.
[3] Ambros V. The functions of animal microRNAs. Nature, 2004,431(7006):350–5.
[4] Bartel DE. MicroRNAs: Genomics, biogenesis, mechanism and function. Cell,2004,116:281-297.
[5] Konstantin D , Boldin TMP , Chang KJ , Baltimore D. NF-κB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. PNAS, 2006 ,103(33):12482-12486.
[6] Dai R, Phillips RA, Zhang Y, Khan D, Crasta O, Ahmed SA. Suppression of LPS-induced Interferon-gamma and nitric oxide in splenic lymphocytes by select estrogen-regulated microRNAs: a novel mechanism of immune modulation. Blood, 2008;112(12):4591–7.
[7] Nahid MA, Pauley KM, Satoh M, Chan EK. MICRORNA-146A is critical for endotoxin-induced tolerance. Implication on innate immunity. J Biol Chem 2009;284(50):34590–9.
[8] Perry MM, Sterghios A, Williams AE, Shepherd NJ, Larner-Svensson HM, Lindsay MA. Rapid changes in microRNA-146a expression negatively regulate the IL-1β-induced inflammatory response in human lung alveolar epit helial cells. J Immunol , 2008,180(8): 5689-5698.
[9] Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, Taira K, Akira S, Fujita T. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol,2004;5(7):730–7.
[10] Takeuchi O, Akira S. MDA5 ? RIG-I and virus recognition. Curr Opin Immunol,2008;20(1):17–22.
[11] Hou J, Wang P, Lin L, Liu X, Ma F, An H, Wang Z, Cao X. MicroRNA-146a feedback inhibits RIGI-dependent Type I IFN production in macrophages by targeting TRAF6, IRAK1, and IRAK2. type I. J Immunol, 2009;183(3):2150-8.
[12] Labbaye1 C, Spinello1 I, Quaranta1 MT, Pelosi E, Pasquini L, Petrucci E, Biffoni M, Nuzzolo ER, Billi M, FoàR, Brunetti E, Grignani F, Testa U, Peschle C. A three-step pat hway comprising PLZF/ miR-146a/ CXCR4 controls megakaryopoiesis. Nat Cell Biol, 2008,10(7):788-801.
[13] Nakasa T, Miyaki S, Okubo A, Hashimoto M, Nishida K, Ochi M, Asahara H. Expression of microRNA-146 in rheumatoid art hritis synovial tissue. Arthritis Rheum , 2008,58(5): 1284-1292.
[14] Pauley KM, Satoh M, Chan AL, Bubb MR, Reeves WH, Chan EK. Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid art hritis patients. Art hritis Res Ther, 2008,10(4):R101.
[15] Tang Y, Luo X, Cui H, Ni X, Yuan M, Guo Y, Huang X, Zhou H, de Vries N, Tak PP, Chen S, Shen N. MicroRNA-146A contributes to abnormal activation of the typeΙinterferon pathway in human lupus by targeting the key signaling proteins. Art hritis Rheum, 2009, 60(4):1065-1075.
[16] Sonkoly E, Wei T, Janson PC, Saaf A, Lundeberg L, Tengvall-Linder M, Norstedt G, Alenius H, Homey, B, Scheynius A, St?hle M, Pivarcsi A. MicroRNAs: novel regulators involved in the pathogenesis of psoriasis? PLoS One, 2007, 2(7), e610.
[17] He H, Jazdzewski K, Li W, Liyanarachchi S, Nagy R, Volinia S, Calin GA, Liu CG, Franssila K, Suster S, Kloos RT, Croce CM, de la Chapelle A. The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci U SA,2005,102(52):19075-80.
[18] Jazdzewski K, Murray EL, Franssila K, Jarzab B, Schoenberg DR, de la Chapelle A. Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci U S A 2008,105(20):7269-74.
[19] Zhang H, Luo XQ, Zhang P, Huang LB, Zheng YS, Wu J, Zhou H, Qu LH, Xu L, Chen YQ. MicroRNA patterns associated with clinical prognostic parameters and CNS relapse prediction in pediatric acute leukemia. PLoS One, 2009;4(11):e7826.
[20] Young LS, Murray PG. Epstein-Barr virus and oncogenesis: from latent genes to tumours. Oncogene, 2003;22(33):5108–21.
[21] Cameron JE, Yin Q, Fewell C, Lacey M, McBride J, Wang X, Lin Z, Schaefer BC, Flemington EK. Epstein–Barr virus latent membrane protein 1 induces cellular MicroRNA miR-146a, a modulator of lymphocyte signaling pathways. J Virol, 2008;82(4):1946–58.
[22] Xu T, Zhu Y, Wei QK, Yuan Y, Zhou F, Ge YY, Yang JR, Su H, Zhuang SM. A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma. Carcinogenesis, 2008;29(11):2126-31.
[23] Iwai N , Naraba H. Polymorphisms in human pre2miRNA [J ] . Biochem Biophys Res Commun , 2005 ,331 :143921444.
[24] Xu B, Feng NH, Li PC, Tao J, Wu D, Zhang ZD, Tong N, Wang JF, Song NH, Zhang W, Hua LX, Wu HF. A functional polymorphism in Pre-miR-146a gene is associated with prostate cancer risk and mature miR-146a expression in vivo. Prostate 2010; 70: 467-72.
[25] Shen J, Ambrosone CB, DiCioccio RA, Odunsi K, Lele SB, Zhao H. A functional polymorphism in the miR-146a gene and age of familial breast/ovariancancer diagnosis. Carcinogenesis 2008; 29: 1963-6.
[26] Inoue J, Gohda J, Akiyama T, Semba K. NF-kappaB activation in development and progression of cancer. Cancer Sci 2007;98:268–74.
[27] Shevde LA,Samant RS,Goldberg SF,et a1.Suppression of human melan oma metastasis by the metastasis suppressor gene,BRMS1. Exp Cell Res,2002,273(2):229-239.
[28] Meehan WJ,Samant RS,Hopper JE,et a1.Breast cancer metastasis suppressor 1(BRMS1)forms complexes with retinoblastoma-binding protein 1(RBP1)and the mSin3 histone deacetylase complex and represses transcription[J].J Biol Chem,2004,279(2):1562-1569.
[29] Zhang s,Lin QD,Di W.Suppression of human ovarian carcinoma metastasis by the metastasis-suppressor gene,BRMS1[J].Int J Gynecol Cancer.2006.16(2):522-531.
[30] Seraj MI,Harding MA,Gildea JJ,et a1.The relationship of BRMS1 and RhoGD12 gene expression to metastatic potential in lineage related human bladder cancer cell lines[J].Clin Exp Metastasis,2000,18(6):519-525.
[31] Ohta S,Lai EW ,Pang AL.Downregn lation of metastas is suppressor genes in malignant pheochromocytoma[J].Int J Cancer,2005, 114(1):139-143.
[32] Vasyutina E, Lenhard DC, Birchmeier C. Notch function in myogenesis. Cell Cycle 2007;6:1451–4.
[33] Neeper M, Schmidt AM, Brett J, Yan SD, Wang F, Pan YC, Elliston K, Stern D, Shaw A. Cloning and expression of RAGE: a cell surface receptor for advanced glycosylation end products of proteins. J Biol Chem,1992,267(21):14998–5004.
[2] Kelley JR, Duggan JM. Gastric cancer epidemiology and risk factors. J Clin Epidemiol,2003,56(1):1-9.
[3] Wu MS, Chen CJ, Lin JT. Host-environment interactions: their impact on progression from gastric inflammation to carcinogenesis and on development of new approaches to prevent and treat gastric cancer. Cancer Epidemiol Biomarkers Prev,2005,14(8):1878–82.
[4] Zhu H, Yang L, Zhou B, Yu R, Tang N, Wang B. Myeloperoxidase G-463A polymorphism and the risk of gastric cancer: a case-control study. Carcinogenesis, 2006,27(12):2491-2496.
[5] Yang L, Zhu H, Zhou B, Gu H, Yan H, Tang N, Dong H, Sun Q, Cong R, Chen G, Wang B. The Association Between the Survivin C-31G Polymorphism and Gastric Cancer Risk in a Chinese Population. Dig Dis Sci,2009;54(5):1021-1028.
[6] Gu H, Yang L, Sun Q, Zhou B, Tang N, Cong R, Zeng Y, Wang B. Gly82Ser polymorphism of the receptor for advanced glycation end products is associated with an increased risk of gastric cancer in a Chinese population. Clin Cancer Res,2008;14(11):3627-32.
[7] Yang L, Gu HJ, Zhu HJ, et al. Tissue inhibitor of metalloproteinase-2 G-418C polymorphism is associated with an increased risk of gastric cancer in a Chinese population. Eur J Surg Oncol 2008;34(6):636-641.
[8] Gu H, Yang L, Tang N, Zhou B, Zhu H, Sun Q, Cong R, Wang B. Association of endothelin-converting enzyme-1b C-338A polymorphism with gastric cancer risk: a case-control study.Eur J Cancer,2008;44(9):1253-1258.
[1] Ambros V. microRNAs: tiny regulators with great potential. Cell, 2001; 107: 823-826.
[2] Punj V, Matta H, Schamus S, Tamewitz A, Anyang B, Chaudhary PM. Kaposi's sarcoma-associated herpesvirus-encoded viral FLICE inhibitory protein (vFLIP) K13 suppresses CXCR4 expression by upregulating miR-146a. Oncogene,2010,29(12):1835-1844.
[3] Bhaumik D, Scott GK, Schokrpur S, Patil CK, Campisi J, Benz CC. Expression of microRNA-146 suppresses NF-kappaB activity with reduction of metastatic potential in breast cancer cells. Oncogene,2008,27(42):5643-5647.
[4] Pacifico F, Crescenzi E, Mellone S, Iannetti A, Porrino N, Liguoro D, Moscato F, Grieco M, Formisano S, Leonardi A. Nuclear Factor-{kappa}B Contributes to Anaplastic Thyroid Carcinomas through Up-Regulation of miR-146a. J Clin Endocrinol Metab,2010,95(3):1421-1430.
[5] Motsch N, Pfuh1 T, Mrazek J, Barth S, Grasser FA. Epstein-Barr virus-encoded latent membrane protein 1 (LMP1) induces the expression of the cellular microRNA miR-146a. RNA Biol,2007,4(3):131-137.
[6] Labbaye C, Spinello I, Quaranta MT, Pelosi E, Pasquini L, Petrucci E, Biffoni M, Nuzzolo ER, Billi M, FoàR, Brunetti E, Grignani F, Testa U, Peschle C. A three-step pathway comprising PLZF/miR-146a/CXCR controls megakaryopoiesis. Nat Cell Biol,2008,10(7):788-801.
[7] Hurst DR, Edmonds MD, Scott GK, Benz CC, Vaidya KS, Welch DR. Breast cancer metastasis suppressor 1 up-regulates miR-146, which suppresses breast cancer metastasis. Cancer Res,2009,69(4):1279-1283.
[8] Kuang W, Tan J, Duan Y, Duan J, Wang W, Jin F, Jin Z, Yuan X, Liu Y. Cyclic stretch induced miR-146a upregulation delays C2C12 myogenic differentiationthrough inhibition of Numb. Biochem Biophys Res Commun,2009,378(2): 259-263.
[9] Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt RL, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, Harris CC, Croce CM. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A,2006,103(7):2257-2261.
[10] Lin SL, Chiang A, Chang D, Ying SY. Loss of mir-146a function in hormone-refractory prostate cancer. RNA,2008,14(3):417-424.
[11] Wang X, Tang S, Le SY, Lu R, Rader JS, Meyers C, Zheng ZM. Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth. PLoS One,2008,3(7):e2557.
[12] Yang W, Chendrimada TP, Wang Q, Higuchi M, Seeburg PH, Shiekhattar R, Nishikura K. Modulation of microRNA processing and expression through RNA editing by ADAR deaminases. Nat Struct Mol Biol, 2006, 13(1):13-21
[13] Iwai N , Naraba H. Polymorphisms in human pre-miRNA. Biochem Biophys Res Commun,2005,331(4):1439-1444.
[14] Jazdzewski K, Murray EL, Franssila K, Jarzab B, Schoenberg DR, de la Chapelle A. Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci U S A,2008,105(20):7269-7274.
[15] Xu T, Zhu Y, Wei QK, et al. A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma. Carcinogenesis,2008,29(11):2126-2131.
[16] Xu B, Feng NH, Li PC, Tao J, Wu D, Zhang ZD, Tong N, Wang JF, Song NH, Zhang W, Hua LX, Wu HF. A functional polymorphism in Pre-miR-146a gene isassociated with prostate cancer risk and mature miR-146a expression in vivo. Prostate,2010,70(5):467-472.
[17] Shen J, Ambrosone CB, DiCioccio RA, Odunsi K, Lele SB, Zhao H. A functional polymorphism in the miR-146a gene and age of familial breast/ovarian cancer diagnosis. Carcinogenesis,2008,29(10):1963-1966.
[18] Hu Z, Liang J, Wang Z, Tian T, Zhou X, Chen J, Miao R, Wang Y, Wang X, Shen H. Common genetic variants in pre-microRNAs were associated with increased risk of breast cancer in Chinese women. Hum Mutat,2009,30(1):79-84.
[19] Sobin LH, Wittekind CH. editors. TNM classification of malignant tumors. 5th ed. New York: Wiley & Sons, Inc,1997.59–62.
[20] Wang L, Wei D, Huang S, Peng Z, Le X, Wu TT, Yao J, Ajani J, Xie K. Transcription factor Sp1 expression is a significant predictor of survival in human gastric cancer. Clin Cancer Res, 2003, 9(17):6371-6380.
[21] Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, Iorio MV, Visone R, Sever NI, Fabbri M, Iuliano R, Palumbo T, Pichiorri F, Roldo C, Garzon R, Sevignani C, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med, 2005, 353(17):1793-1801.
[22] Raveche ES, Salerno E, Scaglione BJ, Manohar V, Abbasi F, Lin YC, Fredrickson T, Landgraf P, Ramachandra S, Huppi K, Toro JR, Zenger VE, Metcalf RA, Marti GE. Abnormal microRNA-16 locus with synteny to human 13q14 linked to CLL in NZB mice. Blood, 2007, 109(12):5079-5086.
[23] Zeng Y, Yi R, Cullen BR. Recognition and cleavage of primary microRNA precursors by the nuclear processing enzyme Drosha. EMBO J, 2005, 24(1):138-148.
[24] Zeng Y, Cullen BR. Sequence requirements for micro RNA processing and function in human cells. RNA, 2003, 9(1):112-123.
[25] Karin M. NF-kappaB as a critical link between inflammation and cancer. Cold Spring Harbor Perspect Biol, 2009,1(5):a000141.
[26] Naugler WE, Karin M. NF-kappaB and cancer-identifying targets and mechanisms. Curr Opin Genet Dev, 2008,18(1):19-26.
[27] Nahid MA, Pauley KM, Satoh M, Chan EK. miR-146a is critical for endotoxin-induced tolerance: IMPLICATION IN INNATE IMMUNITY. J Biol Chem, 2009, 284(50):34590-34599.
[28] Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A, 2006,103(33):12481-12486.
[29] Cameron JE, Yin Q, Fewell C, Lacey M, McBride J, Wang X, Lin Z, Schaefer BC, Flemington EK. Epstein-Barr virus latent membrane protein 1 induces cellular MicroRNA miR-146a, a modulator of lymphocyte signaling pathways. J Virol, 2008,82(4): 1946-1958.
[30] Nakasa T, Miyaki S, Okubo A, Hashimoto M, Nishida K, Ochi M, Asahara H. Expression of microRNA-146 in rheumatoid arthritis synovial tissue. Arthritis Rheum, 2008, 58(5): 1284-1292.
[31] Stanczyk J, Pedrioli DM, Brentano F, Sanchez-Pernaute O, Kolling C, Gay RE, Detmar M, Gay S, Kyburz D. Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis. Arthritis Rheum, 2008, 58(4): 1001-1009.
[32] Ruan K, Fang X, Ouyang G. MicroRNAs: novel regulators in the hallmarks of human cancer. Cancer Lett, 2009, 285(2): 116-126.
[33] Rehmsmeier M, Steffen P, Hochsmann M, Giegerich R. Fast and effectiveprediction of microRNA/target duplexes. RNA, 2004, 10(10): 1507-1517.
[34] Jazdzewski K, Murray EL , Murray KF , et al . Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci U S A,2008,105(20):7269-7274.
[35] Zhu H, Yang L, Zhou B, Yu R, Tang N, Wang B. Myeloperoxidase G-463A polymorphism and the risk of gastric cancer: a case-control study. Carcinogenesis,2006, 27(12):2491-2496.
[36] Parkin DM. International variation. Oncogene, 2004,23(38):6329-40.
[37] Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin,2005,55(2):74-108.
[1] Leng L, Bucala R. Macrophage migration inhibitory factor. Crit Care Med, 2005, 33(12 Suppl): S475-S477.
[2] Bach JP, Rinn B, Meyer B, Dodel R, Bacher M. Role of MIF in inflammation and tumorigenesis. Oncology,2008, 75(3-4):127-133.
[3] Bucala R, Donnelly SC. Macrophage migration inhibitory factor: a probable link between inflammation and cancer. Immunity, 2007, 26(3): 281-285.
[4] Calandra T, Roger T. Macrophage migration inhibitory factor: a regulator of innate immunity. Nat Rev Immunol, 2003;3(10): 791-800.
[5] De Jong YP, Abadia-Molina AC, Satoskar AR, Clarke K, Rietdijk ST, Faubion WA, Mizoguchi E, Metz CN, Alsahli M, ten Hove T, Keates AC, Lubetsky JB, Farrell RJ, Michetti P, van Deventer SJ, Lolis E, David JR, Bhan AK, Terhorst C. Development of chronic colitis is dependent on the cytokine MIF. Nat Immunol, 2001,2(11):1061–1066.
[6] Shimizu T, Nishihira J, Mizue Y, Nakamura H, Abe R, Watanabe H, Ohkawara A, Shimizu H. High macrophage migration inhibitory factor (MIF) serum levels associated with extended psoriasis. J Invest Dermatol, 2001,116(6):989–990.
[7] Leech M, Metz C, Hall P, Hutchinson P, Gianis K, Smith M, Weedon H, Holdsworth SR, Bucala R, Morand EF. Macrophage migration inhibitory factor in rheumatoid arthritis: evidence of proinflammatory function and regulation by glucocorticoids. Arthritis Rheum, 1999,42(8):1601–1608.
[8] Repp AC, Mayhew ES, Apte S, Niederkorn JY. Human uveal melanoma cells produce macrophage migration-inhibitory factor to prevent lysis by NK cells. J Immunol, 2000;165(2):710–715.
[9] Akbar SM, Abe M, Murakami H, Tanimoto K, Kumagi T, Yamashita Y, Michitaka K, Horiike N, Onji M. Macrophage migration inhibitory factor inhepatocellular carcinoma and liver cirrhosis: relevance to pathogenesis. Cancer Lett, 2001;171(2):125–132.
[10] He XX, Yang J, Ding YW, Liu W, Shen QY, Xia HH. Increased epithelial and serum expression of m acrophage migration inhibitory factor (MIF) in gastric cancer:potential role of M IF in gastric carcinogenesis.Gut,2006,55(6):797-802.
[11] Shun CT, Lin JT, Huang SP, Lin MT, Wu MS. Expression of macrophage migration inhibitory factor is associated with enhanced angiogenesis and advanced stage in gastric carcinomas.World J Gastroenterol,2005,11(24):3767-3771.
[12] Donn R, Alourfi Z, De Benedetti F, Meazza C, Zeggini E, Lunt M, Stevens A, Shelley E, Lamb R, Ollier WE, Thomson W, Ray D; British Paediatric Rheumatology Study Group. Mutation screening of the macrophage migration inhibitory factor gene: positive association of a functional polymorphism of macrophage migration inhibitory factor with juvenile idiopathic arthritis.Arthritis Rheum, 2002: 46(9): 2402–2409.
[13] Baugh JA, Chitnis S, Donnelly SC, Monteiro J, Lin X, Plant BJ, Wolfe F, Gregersen PK, Bucala R. Afunctional promoter polymorphism in the macrophage migration inhibitory factor (MIF) gene associated with disease severity in rheumatoid arthritis. Genes Immun, 2002, 3(3): 170–176.
[14] Sanchez E, Gomez LM, Lopez-Nevot MA, Sabio JM, Ortego-Centeno N, de Ramón E, Anaya JM, González-Escribano MF, Koeleman BP, Martín J. Evidence of association of macrophage migration inhibitory factor gene polymorphisms with systemic lupus erythematosus. Genes Immun, 2006, 7(5): 433–436.
[15] Awandare GA, Ouma C, Keller CC, Were T, Otieno R, Ouma Y, Davenport GC, Hittner JB, Ong'echa JM, Ferrell R, Perkins DJ. A macrophage migrationinhibitory factor promoter polymorphism is associated with high-density parasitemia in children with malaria. Genes Immun, 2006, 7(7): 568-575.
[16] Donn R, Alourfi Z, De Benedetti F, Meazza C, Zeggini E, Lunt M, Stevens A, Shelley E, Lamb R, Ollier WE, Thomson W, Ray D; British Paediatric Rheumatology Study Group. Mutation screening of the macrophage migration inhibitory factor gene. Arthritis Rheum, 2002, 46(9): 2402 - 2409.
[17] Gómez LM, Sánchez E, Ruiz-Narvaez EA, López-Nevot MA, Anaya JM, Martín J. Macrophage migration inhibitory factor gene influences the risk of developing tuberculosis in northwestern Colombian population. Tissue Antigens, 2007,70(1):28-33.
[18] Ding GX, Zhou SQ, Xu Z, Feng NH, Song NH, Wang XJ, Yang J, Zhang W, Wu HF, Hua LX. The Association Between MIF-173 G>C Polymorphism and Prostate Cancer in Southern Chinese. Journal of Surgical Oncology, 2009,100(2):106–110.
[19] Xue Y, Xu H, Rong L, Lu Q, Li J, Tong N, Wang M, Zhang Z, Fang Y. The MIF -173G/C polymorphism and risk of childhood acute lymphoblastic leukemia in a Chinese population. Leuk Res. 2010 May 4.
[20] de la Fontaine L, Schwarz MJ, Riedel M, Dehning S, Douhet A, Spellmann I, Kleindienst N, Zill P, Plischke H, Gruber R, Müller N. Investigating disease susceptibility and the negative correlation of schizophrenia and rheumatoid arthritis focusing on MIF and CD14 gene polymorphisms. Psychiatry Res, 2006,30;144(1):39-47
[21] Donn RP, Shelley E, Ollier WE, Thomson W; British Paediatric Rheumatology Study Group. A novel 5'-flanking region polymorphism of macrophage migration inhibitory factor is associated with systemic-onset juvenile idiopathic arthritis. Arthritis Rheum. 2001,44(8):1782-1785.
[22] Sun HW,Bernhagen J,Bucala R,Lolis E. Crystal structure at 2.6-A resolution of human macrophage migration inhibitory factor. Proc NatlAcad Sci USA, 1996,93(11):5191-5196.
[23] Baugh J A, Bucala R. Macrophage migration inhibitory factor. J CritCare Med,2002,30(1 Supp):27-35.
[24] Bernhagen J, Calandra T, Mitchell RA, Martin SB, Tracey KJ, Voelter W, Manogue KR, Cerami A, Bucala R. Nature, 1993, 365(6448):756-759.
[25] Bucala R. MIF, a previously unrecognized pituitary hormone and macrophage cytokine,is a pivotal mediator in endotoxie shock. Circulation Shock, 1994, 44(1):35-39.
[26] Calandra T, Bernhagen J, Mitchell RA, Bucala R. The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor. Exp Med, 1994,179(6):1895-1902.
[27] Bacher M, Metz CN, Calandra T, Mayer K, Chesney J, Lohoff M, Gemsa D, Donnelly T, Bucala R. An essential regulatory role for macrophage migration inhibitory factor in T-cell activation. Proc Natl Acad Sci U S A, 1996;93(15):7849-7854.
[28] Calandra T, Bernhagen J, Metz CN, Spiegel LA, Bacher M, Donnelly T, Cerami A, Bucala R. MIF as a glucocorticoid-induced modulator of cytokine production. Nature, 1995;377(6544):68-71.
[29] Xia HH, Lam SK, Huang XR, Wong WM, Leung SY, Yuen ST, Lan HY, Wong BC. Helicobacter pylori infection is associated with increased expression of macrophage migratory inhibitory factor--by epithelial cells, T cells, and macrophages--in gastric mucosa. J Infect Dis, 2004; 190(2): 293-302.
[30] Mitchell RA. Mechanisms and effectors of MIF-dependent promotion of tumourigenesis. Cell Signal, 2004; 16(1): 13-19.
[31] Lue H, Kapurniotu A, Fingerle-Rowson G, Roger T, Len L, Thiele M, Calandra T, Bucala R, Bernhagen J. Rapid and transient activation of the ERK MAPK signalling pathway by macrophage migration inhibitory factor (MIF) and dependence on JAB1/CSN5 and Src kinase activity. Cell Signal, 2006, 18(5):688-703.
[32] Lue H, Thiele M, Franz J, Dahl E, Speckgens S, Leng L, Fingerle-Rowson G, Bucala R, Lüscher B, Bernhagen J. Macrophage migration inhibitory factor (MIF) promotes cell survival by activation of the Akt pathway and role for CSN5/JAB1 in the control of autocrine MIF activity. Oncogene, 2007, 26(35): 5046-5059.
[33] Petrenko O, Moll UM. Macrophage migration inhibitory factor MIF interferes with the Rb-E2F pathway. Mol Cell, 2005, 17(2): 225-236.
[34] Li GQ, Xie J, Lei XY, Zhang L. Macrophage migration inhibitory factor regulates proliferation of gastric cancer cells via the PI3K/Akt pathway. World J Gastroenterol, 2009,15(44):5541-5548.
[35] Yu BH, Zhou XY. Advances on PI3K/Akt/mTOR signalling pathway in malignancies. Zhonghua Binglixue Zazhi, 2005, 34(10):674-676.
[36] Tokunaga E, Oki E, Egashira A, Sadanaga N, Morita M, Kakeji Y, Maehara Y. Deregulation of the Akt pathway in human cancer. Curr Cancer Drug Targets, 2008, 8(1): 27-36.
[37] Michl P, Downward J. Mechanisms of disease: PI3K/AKT signaling in gastrointestinal cancers. Z Gastroenterol, 2005,43(10): 1133-1139.
[38] Metz CN , Bucala R. Role of macrophage migration inhibitory factor in the regulation of the immune response. Adv Immunol, 1997, 66 (3):197-223.
[39] Miechell RA, Bucala R. Tumor growth promoting properties of macrophage migration inhibitory factor (MIF). Semin Cancer Biol , 2000, 10 (5): 359-366.
[40] Hudson JD, Shoaibi MA , Maestro R, Carnero A, Hannon GJ, Beach DH. Aproinflammatory cytokine inhibits p53 tumor suppressor activity. J Exp Med, 1999, 190 (10): 1375-1382.
[1] Gangaraju VK, Lin H. MicroRNAs: key regulators of stem cells. Nat Rev Mol Cell Biol, 2009,10(2):116–25.
[2] Asli NS, Pitulescu ME, Kessel M. MicroRNAs in organogenesis and disease. Curr Mol Med, 2008,8(8):698–710.
[3] Ambros V. The functions of animal microRNAs. Nature, 2004,431(7006):350–5.
[4] Bartel DE. MicroRNAs: Genomics, biogenesis, mechanism and function. Cell,2004,116:281-297.
[5] Konstantin D , Boldin TMP , Chang KJ , Baltimore D. NF-κB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. PNAS, 2006 ,103(33):12482-12486.
[6] Dai R, Phillips RA, Zhang Y, Khan D, Crasta O, Ahmed SA. Suppression of LPS-induced Interferon-gamma and nitric oxide in splenic lymphocytes by select estrogen-regulated microRNAs: a novel mechanism of immune modulation. Blood, 2008;112(12):4591–7.
[7] Nahid MA, Pauley KM, Satoh M, Chan EK. MICRORNA-146A is critical for endotoxin-induced tolerance. Implication on innate immunity. J Biol Chem 2009;284(50):34590–9.
[8] Perry MM, Sterghios A, Williams AE, Shepherd NJ, Larner-Svensson HM, Lindsay MA. Rapid changes in microRNA-146a expression negatively regulate the IL-1β-induced inflammatory response in human lung alveolar epit helial cells. J Immunol , 2008,180(8): 5689-5698.
[9] Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, Taira K, Akira S, Fujita T. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol,2004;5(7):730–7.
[10] Takeuchi O, Akira S. MDA5 ? RIG-I and virus recognition. Curr Opin Immunol,2008;20(1):17–22.
[11] Hou J, Wang P, Lin L, Liu X, Ma F, An H, Wang Z, Cao X. MicroRNA-146a feedback inhibits RIGI-dependent Type I IFN production in macrophages by targeting TRAF6, IRAK1, and IRAK2. type I. J Immunol, 2009;183(3):2150-8.
[12] Labbaye1 C, Spinello1 I, Quaranta1 MT, Pelosi E, Pasquini L, Petrucci E, Biffoni M, Nuzzolo ER, Billi M, FoàR, Brunetti E, Grignani F, Testa U, Peschle C. A three-step pat hway comprising PLZF/ miR-146a/ CXCR4 controls megakaryopoiesis. Nat Cell Biol, 2008,10(7):788-801.
[13] Nakasa T, Miyaki S, Okubo A, Hashimoto M, Nishida K, Ochi M, Asahara H. Expression of microRNA-146 in rheumatoid art hritis synovial tissue. Arthritis Rheum , 2008,58(5): 1284-1292.
[14] Pauley KM, Satoh M, Chan AL, Bubb MR, Reeves WH, Chan EK. Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid art hritis patients. Art hritis Res Ther, 2008,10(4):R101.
[15] Tang Y, Luo X, Cui H, Ni X, Yuan M, Guo Y, Huang X, Zhou H, de Vries N, Tak PP, Chen S, Shen N. MicroRNA-146A contributes to abnormal activation of the typeΙinterferon pathway in human lupus by targeting the key signaling proteins. Art hritis Rheum, 2009, 60(4):1065-1075.
[16] Sonkoly E, Wei T, Janson PC, Saaf A, Lundeberg L, Tengvall-Linder M, Norstedt G, Alenius H, Homey, B, Scheynius A, St?hle M, Pivarcsi A. MicroRNAs: novel regulators involved in the pathogenesis of psoriasis? PLoS One, 2007, 2(7), e610.
[17] He H, Jazdzewski K, Li W, Liyanarachchi S, Nagy R, Volinia S, Calin GA, Liu CG, Franssila K, Suster S, Kloos RT, Croce CM, de la Chapelle A. The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci U SA,2005,102(52):19075-80.
[18] Jazdzewski K, Murray EL, Franssila K, Jarzab B, Schoenberg DR, de la Chapelle A. Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci U S A 2008,105(20):7269-74.
[19] Zhang H, Luo XQ, Zhang P, Huang LB, Zheng YS, Wu J, Zhou H, Qu LH, Xu L, Chen YQ. MicroRNA patterns associated with clinical prognostic parameters and CNS relapse prediction in pediatric acute leukemia. PLoS One, 2009;4(11):e7826.
[20] Young LS, Murray PG. Epstein-Barr virus and oncogenesis: from latent genes to tumours. Oncogene, 2003;22(33):5108–21.
[21] Cameron JE, Yin Q, Fewell C, Lacey M, McBride J, Wang X, Lin Z, Schaefer BC, Flemington EK. Epstein–Barr virus latent membrane protein 1 induces cellular MicroRNA miR-146a, a modulator of lymphocyte signaling pathways. J Virol, 2008;82(4):1946–58.
[22] Xu T, Zhu Y, Wei QK, Yuan Y, Zhou F, Ge YY, Yang JR, Su H, Zhuang SM. A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma. Carcinogenesis, 2008;29(11):2126-31.
[23] Iwai N , Naraba H. Polymorphisms in human pre2miRNA [J ] . Biochem Biophys Res Commun , 2005 ,331 :143921444.
[24] Xu B, Feng NH, Li PC, Tao J, Wu D, Zhang ZD, Tong N, Wang JF, Song NH, Zhang W, Hua LX, Wu HF. A functional polymorphism in Pre-miR-146a gene is associated with prostate cancer risk and mature miR-146a expression in vivo. Prostate 2010; 70: 467-72.
[25] Shen J, Ambrosone CB, DiCioccio RA, Odunsi K, Lele SB, Zhao H. A functional polymorphism in the miR-146a gene and age of familial breast/ovariancancer diagnosis. Carcinogenesis 2008; 29: 1963-6.
[26] Inoue J, Gohda J, Akiyama T, Semba K. NF-kappaB activation in development and progression of cancer. Cancer Sci 2007;98:268–74.
[27] Shevde LA,Samant RS,Goldberg SF,et a1.Suppression of human melan oma metastasis by the metastasis suppressor gene,BRMS1. Exp Cell Res,2002,273(2):229-239.
[28] Meehan WJ,Samant RS,Hopper JE,et a1.Breast cancer metastasis suppressor 1(BRMS1)forms complexes with retinoblastoma-binding protein 1(RBP1)and the mSin3 histone deacetylase complex and represses transcription[J].J Biol Chem,2004,279(2):1562-1569.
[29] Zhang s,Lin QD,Di W.Suppression of human ovarian carcinoma metastasis by the metastasis-suppressor gene,BRMS1[J].Int J Gynecol Cancer.2006.16(2):522-531.
[30] Seraj MI,Harding MA,Gildea JJ,et a1.The relationship of BRMS1 and RhoGD12 gene expression to metastatic potential in lineage related human bladder cancer cell lines[J].Clin Exp Metastasis,2000,18(6):519-525.
[31] Ohta S,Lai EW ,Pang AL.Downregn lation of metastas is suppressor genes in malignant pheochromocytoma[J].Int J Cancer,2005, 114(1):139-143.
[32] Vasyutina E, Lenhard DC, Birchmeier C. Notch function in myogenesis. Cell Cycle 2007;6:1451–4.
[33] Neeper M, Schmidt AM, Brett J, Yan SD, Wang F, Pan YC, Elliston K, Stern D, Shaw A. Cloning and expression of RAGE: a cell surface receptor for advanced glycosylation end products of proteins. J Biol Chem,1992,267(21):14998–5004.