乳腺癌组织中miR-21的表达及意义
摘要
目的:对乳腺癌组织及其相应癌旁组织中miR-21进行定量检测,分析其表达与临床病理特征的及意义。
方法:采用茎环实时荧光逆转录聚合酶链反应(RT-PCR)检测60例乳腺癌及其对应癌旁组织中miR-21的表达量,分析其表达与肿瘤大小、TNM分期、组织学类型、淋巴结转移、雌激素受体(ER)、孕激素受体(PR)等临床病理特征的关系。
结果:实时RT-PCR方法检测miR-21表达的敏感性和特异性良好。miR-21在乳腺癌组织中的表达明显高于癌旁组织(P < 0.001 );miR-21的高表达还与较高的TNM分期,淋巴结转移及PR的表达程度有关(各分组间P<0.01及< 0.05);miR-21的表达在“三阴性乳腺癌”(ER,PR,CerbB-2均为阴性)和“非三阴性乳腺癌”之间的表达存在统计学差异(P=0.029)。
结论:miR-21在乳腺癌组织中高表达,其水平可能与乳腺癌的恶性程度有关。
Objective:To examine the level of expression of microRNA-21 in breast cancer and normal tissues more than 5 cm away from the tumor tissues , The association of miR-21 expression with the clinical pathological factors of breast cancer were analyzed .
Methods:Specimens of breast cancer and normal tissues more than 5cm away from the tumor tissues were collected from 60 patients, The miR-21 expression was detected by Stem-loop real-time RT-PCR . Levels of miR-21 expression by tumor size, TNM clinical stage, histology, lymph node involvement, hormone receptor status were compared .
Results:High sensitivity, specificity and precision of Stem-loop real-time RT-PCR allows for direct analysis of expression of miR-21 of breast cancer . With normal tissues, obvious high level of expression of miR-21 was detected (P < 0.001 ),Elevated miR-21 expression was also positively correlated with Advanced TNM stage, lymph node metastasis, and low PR levels(P =0.007,0.001,and 0.012 respectively), Moreover, We discover for first time ,levels of expression of miR-21 in triple-negative breast cancer(TNBC)is high than other types(P =0.029).
Conclusion:High levels of expression of miR-21 are correlated with malignant degree of breast cancer.
方法:采用茎环实时荧光逆转录聚合酶链反应(RT-PCR)检测60例乳腺癌及其对应癌旁组织中miR-21的表达量,分析其表达与肿瘤大小、TNM分期、组织学类型、淋巴结转移、雌激素受体(ER)、孕激素受体(PR)等临床病理特征的关系。
结果:实时RT-PCR方法检测miR-21表达的敏感性和特异性良好。miR-21在乳腺癌组织中的表达明显高于癌旁组织(P < 0.001 );miR-21的高表达还与较高的TNM分期,淋巴结转移及PR的表达程度有关(各分组间P<0.01及< 0.05);miR-21的表达在“三阴性乳腺癌”(ER,PR,CerbB-2均为阴性)和“非三阴性乳腺癌”之间的表达存在统计学差异(P=0.029)。
结论:miR-21在乳腺癌组织中高表达,其水平可能与乳腺癌的恶性程度有关。
Objective:To examine the level of expression of microRNA-21 in breast cancer and normal tissues more than 5 cm away from the tumor tissues , The association of miR-21 expression with the clinical pathological factors of breast cancer were analyzed .
Methods:Specimens of breast cancer and normal tissues more than 5cm away from the tumor tissues were collected from 60 patients, The miR-21 expression was detected by Stem-loop real-time RT-PCR . Levels of miR-21 expression by tumor size, TNM clinical stage, histology, lymph node involvement, hormone receptor status were compared .
Results:High sensitivity, specificity and precision of Stem-loop real-time RT-PCR allows for direct analysis of expression of miR-21 of breast cancer . With normal tissues, obvious high level of expression of miR-21 was detected (P < 0.001 ),Elevated miR-21 expression was also positively correlated with Advanced TNM stage, lymph node metastasis, and low PR levels(P =0.007,0.001,and 0.012 respectively), Moreover, We discover for first time ,levels of expression of miR-21 in triple-negative breast cancer(TNBC)is high than other types(P =0.029).
Conclusion:High levels of expression of miR-21 are correlated with malignant degree of breast cancer.
引文
[1] Thomas D,Kenneth J.Analyzing real-time PCR data by the comparative CT method[J].Nature Protocols, 2008, 3(6):1101-1108.
[2] Liu JD,Valencia-Sanchez MA,Hannon GJ ,et a1 . MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies[J].Nat Cell Biol,2005,7(7):719-723.
[3] He L,Hannon GJ.MicroRNAs:small RNAs with a big role in gene regulation[J].Nat Rev Genet,2004,5(7):522-531.
[4] Bartel DP.MicroRNAs:genomics, biogenesis, mechanism, and function [J].Cell,2004,116 (2):281-297.
[5] Calin GA, Sevignani C, Dumitru CD,et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers [J]. PNAS,2004,101(9):2399-3004.
[6] Calin GA,Dumitru CD,Shimizu M,et al . Frequent deletions and down-regulation of microRNA genes miR15 and miR16 at 13q14 in chromic lymphocyticleukemia [J]. PNAS, 2002,99(24):15524-15529.
[7] Volinia S,Calin GA,Liu C G,et a1.A microRNA expression signature of human solid tumors defines cancer gene targets[J].Proc Natl Acad Sci U S A,2006,103(7):2257-2261.
[8] Meng F, Henson R, Wehbe-Janek H,et al. MicorRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer[J].Gastroenterology,2007,133(2):647-658.
[9] Zhu S,Si ML,Wu H,et al.MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1)[J].J Biol Chem,2007,282(19):14328-14336.
[10] Frankel LB,Christoffersen NR,Jacobsen A,et al. Programmed Cell Death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells[J].J Biol Chem,2008,283(2):1026-1033.
[11] Hammond S M. microRNA detection comes of age[J]. Nature Methods, 2006, 3(1): 12-13.
[12] lorio M V, Fen'acin M , Liu C G , et a1. MicroRNA gene
[13] expression deregulation in human breast cancer. Cancer Res 2005,65:7065—7070.
[14] Mattie M D,Benz C C,Bowers J,et a1. Optimized high throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies. Mol Cancer,2006,5:24.
[15] Tavazoie S F,Alarcon C, Oskarsson T,et a1. Endogenous humna microRNAs that suppress breast cancer metastasis Nature,2008,451:147—152.
[16] Li-Xu Yan,Xiu-Fang Huang,Qiong Shao,et al. MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage,lymph node metastasis and patient poor prognosis[J].RNA,2008,14(11):2348-2360.
[17] Qian B,Katsaros D,Lu L,et al.High miR-21 expression in breast cancer associated with poor disease-free survival in early stage disease and high TCF- beta1[J]. Breast Cancer Res Treat,2009,117(1): 1781-96
[1] Lee RC,Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14[J].Cell 75:843-854
[2] Ji R , Cheng Y , Yue J , et al . MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation [J] .Circ Res , 2007 ,100(11) :1537 - 1539
[3] Lee Y, Kim M, Han J, et al . MicroRNA genes are transcribed by RNA polymerase II[J]. EMBO J 2004;23:4051– 60
[4] Lee Y, Han J, Yeom KH, et al . Drosha in primary microRNA processing[J]. Cold Spring Harb Symp Quant Biol 2006;71:51–7
[5] Lee Y, Ahn C, Han J, et al.The nuclear RNase III Drosha initiates microRNA processing[J]. Nature 2003;425:415–9
[6] Liu JD,Valencia-Sanchez MA,Hannon GJ,et a1.MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies[J].Nat Cell Biol,2005,7(7):719-723.
[7] He L , Hannon GJ . MicroRNAs : small RNAs with a big role in gene regulation[J].Nat Rev Genet,2004,5(7):522-531
[8] Calin GA, Ferracin M, Cimmino A, et al. A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia[J]. N Engl J Med 2005;353:1793– 801; erratum 2006;355:533
[9] Iorio MV, Ferracin M, Liu CG , et al. MicroRNA gene expression deregulation in human breast cancer[J]. Cancer Res 2005;65:7065–70
[10] Diaz LK, Zhou X, Wright ET, et al. CD44 expression is associated with increased survival in node-negative invasive breast carcinoma [ J ] Clin Cancer Res 2005;11:3309–14
[11]Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer[J]. Nature 2007;449:682– 8
[12]Perry SV. Vertebrate tropomyosin: distribution properties and function[J]. J Muscle Res Cell Motil 2001;22:5– 49
[13] Hossain A, Kuo MT, Saunders GF. Mir-17–5p regulates breast cancer cellproliferation by inhibiting translation of AIB1 mRNA[J]. Mol Cell Biol 2006;26:8191–201
[14] Yu Z, Wang C, Wang M, et al. A cyclin D1/microRNA 17/20 regulatory feedback loop in control of breast cancer cell proliferation[J]. J Cell Bio 2008;182:509–17
[15] Tavazoie SF, Alarcon C, Oskarsson T, et al. Endogenous human microRNAs that suppress breast cancer metastasis[J]. Nature 2008;451:147–52
[16] Adams BD, Furneaux H, White BA. The microribonucleic acid (miRNA) miR-206 targets the human estrogen receptor- (ER_) and represses ER_ messenger RNA and protein expression in breast cancer cell lines[J]. J Mol Endocrinol 2007;21:1132– 47
[17] Wang M, Tan LP, Dijkstra MK, et al. miRNA analysis in B-cell chronic lymphocytic leukaemia: proliferation centres characterized by low miR-150 and high BIC/miR-155 expression[J]J Pathol 2008;215:13–20
[18] Calin GA, Ferracin M, Cimmino A, et al. A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia[J]. N Engl J Med 2005;353:1793– 801; erratum 2006;355:533
[19] Fulci V, Chiaretti S, Goldoni M,et al. Quantitative technologies establish a novel microRNA profile of chronic lymphocytic leukemia[J]. Blood 2007;109:4944–51
[20] Cimmino A, Calin GA, Fabbri M, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2 [ J ] . Proc Natl Acad Sci U S A 2005;102:13944–9; erratum2006;103:2464
[21] Akao Y, Nakagawa Y, Kitade Y, et al .Downregulation of microRNAs-143 and _145 in B-cell malignancies[J]. Cancer Sci 2007;98:1914–20
[22] Eis PS, Tam W, Sun L, et al. Accumulation of miR-155 and BIC RNA in human B cell lymphomas[J]. Proc Natl Acad Sci U S A, 2005;102:3627–32
[23] Cummins JM, He Y, Leary RJ, et al. The colorectal microRNAome[J]. Proc Natl Acad Sci U S A 2006;103:3687–92
[24] Nagel R, le Sage C, Diosdado B, et al. Regulation of the adenomatous polyposis coli gene by the miR-135 family in colorectal cancer [ J ] .Cancer Res 2008;68:5795–802
[25] Akao Y, Nakagawa Y, Naoe T. MicroRNA-143 and _145 in colon cancer[J]. DNACell Biol 2007;26:311–20.
[26] Guo C, Sah JF, Beard L, et al The noncoding RNA, miR-126, suppresses the growth of neoplastic cells by targeting phosphatidylinositol 3-kinase signaling and is frequently lost in colon cancers [ J ] .Genes Chromosomes Cancer 2008;47:939–46.
[27] Bandre′s E, Cubedo E, Agirre X, et al. Identification by realtime PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues[J]. Mol Cancer 2006;5:29.
[28] Lanza G, Ferracin M, Gafa` R, et al. mRNA/microRNA gene expression profile in microsatellite unstable colorectal cancer[J]. Mol Cancer 2007;6:54.
[29] Murakami Y, Yasuda T, Saigo K,et al. Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues[J]. Oncogene 2006;25:2537– 45.
[30] Ladeiro Y, Couchy G, Balabaud C, et al. MicroRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations[J]. Hepatology 2008;47:1955– 63.
[31] Li W, Xie L, He X, et al. Diagnostic and prognostic implications of micro-RNAs in human hepatocellular carcinoma[J]. Int J Cancer 2008;123:1616–22.
[32] Jiang J, Gusev Y, Aderca I,et al. Association of microRNA expression in hepatocellular carcinomas with hepatitis infection, cirrhosis, and patien survival[J].Clin Can Res 2008;14:419–27.
[33] Fornari F, Gramantieri L, Ferracin M, et al. miR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma[J]. Oncogene 2008;27:5651– 61.
[34] Roush S, Slack FJ. The let-7 family of microRNAs[J]. Trends Cell Biol 2008;18:505–16.
[35] Johnson SM, Grosshans H, Shingara J, et al. RAS is regulated by the let-7 microRNA family[J]. Cell 2005;120:635– 47.
[36] Kumar MS, Erkeland SJ, Pester RE, et al. Suppression of non-small cell lung tumor development by the let-7 microRNA family[J]. Proc Natl Acad Sci U S A 2008;105:3903–8.
[37] Weiss GJ, Bemis LT, Nakajima E,et al. EGFR regulation by microRNA in lungcancer: correlation with clinical response and survival to gefitinib and EGFR expression in cell lines[J]. Ann Oncol 2008;19:1053–9.
[38] Yu SL, Chen HY, Chang GC, et al. MicroRNA signature predicts survival and relapse in lung cancer[J]. Cancer Cell 2008;13:48–57.
[39] Baskerville S, Bartel DP. Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes[J]. RNA 2005; 11:241–7.
[40] Szafranska AE, Davison TS, John J, et al. MicroRNA expression alterations are linked to tumorigenesis and nonneoplastic processes in pancreatic ductal adenocarcinoma[J].Oncogene 2007;26:4442–52.
[41] Bloomston M, Frankel WL, Petrocca F,et al. MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis[J]. JAMA 2007;297:1901– 8.
[42] Szafranska AE, Doleshal M, Edmunds HS, et al. Analysis of microRNAs in pancreatic fine-needle aspirates can classify benign and malignant tissues[J]. Clin Chem 2008;54:1716–24.
[43] Porkka KP, Pfeiffer MJ, Waltering KK, et al.MicroRNA expression profiling in prostate cancer[J]. Cancer Res 2007;67:6130–5.
[44] Ozen M, Creighton CJ, Ozdemir M, Widespread deregulation of microRNA expression in human prostate cancer[J]. Oncogene 2008;27:1788–93.
[2] Liu JD,Valencia-Sanchez MA,Hannon GJ ,et a1 . MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies[J].Nat Cell Biol,2005,7(7):719-723.
[3] He L,Hannon GJ.MicroRNAs:small RNAs with a big role in gene regulation[J].Nat Rev Genet,2004,5(7):522-531.
[4] Bartel DP.MicroRNAs:genomics, biogenesis, mechanism, and function [J].Cell,2004,116 (2):281-297.
[5] Calin GA, Sevignani C, Dumitru CD,et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers [J]. PNAS,2004,101(9):2399-3004.
[6] Calin GA,Dumitru CD,Shimizu M,et al . Frequent deletions and down-regulation of microRNA genes miR15 and miR16 at 13q14 in chromic lymphocyticleukemia [J]. PNAS, 2002,99(24):15524-15529.
[7] Volinia S,Calin GA,Liu C G,et a1.A microRNA expression signature of human solid tumors defines cancer gene targets[J].Proc Natl Acad Sci U S A,2006,103(7):2257-2261.
[8] Meng F, Henson R, Wehbe-Janek H,et al. MicorRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer[J].Gastroenterology,2007,133(2):647-658.
[9] Zhu S,Si ML,Wu H,et al.MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1)[J].J Biol Chem,2007,282(19):14328-14336.
[10] Frankel LB,Christoffersen NR,Jacobsen A,et al. Programmed Cell Death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells[J].J Biol Chem,2008,283(2):1026-1033.
[11] Hammond S M. microRNA detection comes of age[J]. Nature Methods, 2006, 3(1): 12-13.
[12] lorio M V, Fen'acin M , Liu C G , et a1. MicroRNA gene
[13] expression deregulation in human breast cancer. Cancer Res 2005,65:7065—7070.
[14] Mattie M D,Benz C C,Bowers J,et a1. Optimized high throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies. Mol Cancer,2006,5:24.
[15] Tavazoie S F,Alarcon C, Oskarsson T,et a1. Endogenous humna microRNAs that suppress breast cancer metastasis Nature,2008,451:147—152.
[16] Li-Xu Yan,Xiu-Fang Huang,Qiong Shao,et al. MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage,lymph node metastasis and patient poor prognosis[J].RNA,2008,14(11):2348-2360.
[17] Qian B,Katsaros D,Lu L,et al.High miR-21 expression in breast cancer associated with poor disease-free survival in early stage disease and high TCF- beta1[J]. Breast Cancer Res Treat,2009,117(1): 1781-96
[1] Lee RC,Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14[J].Cell 75:843-854
[2] Ji R , Cheng Y , Yue J , et al . MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation [J] .Circ Res , 2007 ,100(11) :1537 - 1539
[3] Lee Y, Kim M, Han J, et al . MicroRNA genes are transcribed by RNA polymerase II[J]. EMBO J 2004;23:4051– 60
[4] Lee Y, Han J, Yeom KH, et al . Drosha in primary microRNA processing[J]. Cold Spring Harb Symp Quant Biol 2006;71:51–7
[5] Lee Y, Ahn C, Han J, et al.The nuclear RNase III Drosha initiates microRNA processing[J]. Nature 2003;425:415–9
[6] Liu JD,Valencia-Sanchez MA,Hannon GJ,et a1.MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies[J].Nat Cell Biol,2005,7(7):719-723.
[7] He L , Hannon GJ . MicroRNAs : small RNAs with a big role in gene regulation[J].Nat Rev Genet,2004,5(7):522-531
[8] Calin GA, Ferracin M, Cimmino A, et al. A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia[J]. N Engl J Med 2005;353:1793– 801; erratum 2006;355:533
[9] Iorio MV, Ferracin M, Liu CG , et al. MicroRNA gene expression deregulation in human breast cancer[J]. Cancer Res 2005;65:7065–70
[10] Diaz LK, Zhou X, Wright ET, et al. CD44 expression is associated with increased survival in node-negative invasive breast carcinoma [ J ] Clin Cancer Res 2005;11:3309–14
[11]Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer[J]. Nature 2007;449:682– 8
[12]Perry SV. Vertebrate tropomyosin: distribution properties and function[J]. J Muscle Res Cell Motil 2001;22:5– 49
[13] Hossain A, Kuo MT, Saunders GF. Mir-17–5p regulates breast cancer cellproliferation by inhibiting translation of AIB1 mRNA[J]. Mol Cell Biol 2006;26:8191–201
[14] Yu Z, Wang C, Wang M, et al. A cyclin D1/microRNA 17/20 regulatory feedback loop in control of breast cancer cell proliferation[J]. J Cell Bio 2008;182:509–17
[15] Tavazoie SF, Alarcon C, Oskarsson T, et al. Endogenous human microRNAs that suppress breast cancer metastasis[J]. Nature 2008;451:147–52
[16] Adams BD, Furneaux H, White BA. The microribonucleic acid (miRNA) miR-206 targets the human estrogen receptor- (ER_) and represses ER_ messenger RNA and protein expression in breast cancer cell lines[J]. J Mol Endocrinol 2007;21:1132– 47
[17] Wang M, Tan LP, Dijkstra MK, et al. miRNA analysis in B-cell chronic lymphocytic leukaemia: proliferation centres characterized by low miR-150 and high BIC/miR-155 expression[J]J Pathol 2008;215:13–20
[18] Calin GA, Ferracin M, Cimmino A, et al. A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia[J]. N Engl J Med 2005;353:1793– 801; erratum 2006;355:533
[19] Fulci V, Chiaretti S, Goldoni M,et al. Quantitative technologies establish a novel microRNA profile of chronic lymphocytic leukemia[J]. Blood 2007;109:4944–51
[20] Cimmino A, Calin GA, Fabbri M, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2 [ J ] . Proc Natl Acad Sci U S A 2005;102:13944–9; erratum2006;103:2464
[21] Akao Y, Nakagawa Y, Kitade Y, et al .Downregulation of microRNAs-143 and _145 in B-cell malignancies[J]. Cancer Sci 2007;98:1914–20
[22] Eis PS, Tam W, Sun L, et al. Accumulation of miR-155 and BIC RNA in human B cell lymphomas[J]. Proc Natl Acad Sci U S A, 2005;102:3627–32
[23] Cummins JM, He Y, Leary RJ, et al. The colorectal microRNAome[J]. Proc Natl Acad Sci U S A 2006;103:3687–92
[24] Nagel R, le Sage C, Diosdado B, et al. Regulation of the adenomatous polyposis coli gene by the miR-135 family in colorectal cancer [ J ] .Cancer Res 2008;68:5795–802
[25] Akao Y, Nakagawa Y, Naoe T. MicroRNA-143 and _145 in colon cancer[J]. DNACell Biol 2007;26:311–20.
[26] Guo C, Sah JF, Beard L, et al The noncoding RNA, miR-126, suppresses the growth of neoplastic cells by targeting phosphatidylinositol 3-kinase signaling and is frequently lost in colon cancers [ J ] .Genes Chromosomes Cancer 2008;47:939–46.
[27] Bandre′s E, Cubedo E, Agirre X, et al. Identification by realtime PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues[J]. Mol Cancer 2006;5:29.
[28] Lanza G, Ferracin M, Gafa` R, et al. mRNA/microRNA gene expression profile in microsatellite unstable colorectal cancer[J]. Mol Cancer 2007;6:54.
[29] Murakami Y, Yasuda T, Saigo K,et al. Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues[J]. Oncogene 2006;25:2537– 45.
[30] Ladeiro Y, Couchy G, Balabaud C, et al. MicroRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations[J]. Hepatology 2008;47:1955– 63.
[31] Li W, Xie L, He X, et al. Diagnostic and prognostic implications of micro-RNAs in human hepatocellular carcinoma[J]. Int J Cancer 2008;123:1616–22.
[32] Jiang J, Gusev Y, Aderca I,et al. Association of microRNA expression in hepatocellular carcinomas with hepatitis infection, cirrhosis, and patien survival[J].Clin Can Res 2008;14:419–27.
[33] Fornari F, Gramantieri L, Ferracin M, et al. miR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma[J]. Oncogene 2008;27:5651– 61.
[34] Roush S, Slack FJ. The let-7 family of microRNAs[J]. Trends Cell Biol 2008;18:505–16.
[35] Johnson SM, Grosshans H, Shingara J, et al. RAS is regulated by the let-7 microRNA family[J]. Cell 2005;120:635– 47.
[36] Kumar MS, Erkeland SJ, Pester RE, et al. Suppression of non-small cell lung tumor development by the let-7 microRNA family[J]. Proc Natl Acad Sci U S A 2008;105:3903–8.
[37] Weiss GJ, Bemis LT, Nakajima E,et al. EGFR regulation by microRNA in lungcancer: correlation with clinical response and survival to gefitinib and EGFR expression in cell lines[J]. Ann Oncol 2008;19:1053–9.
[38] Yu SL, Chen HY, Chang GC, et al. MicroRNA signature predicts survival and relapse in lung cancer[J]. Cancer Cell 2008;13:48–57.
[39] Baskerville S, Bartel DP. Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes[J]. RNA 2005; 11:241–7.
[40] Szafranska AE, Davison TS, John J, et al. MicroRNA expression alterations are linked to tumorigenesis and nonneoplastic processes in pancreatic ductal adenocarcinoma[J].Oncogene 2007;26:4442–52.
[41] Bloomston M, Frankel WL, Petrocca F,et al. MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis[J]. JAMA 2007;297:1901– 8.
[42] Szafranska AE, Doleshal M, Edmunds HS, et al. Analysis of microRNAs in pancreatic fine-needle aspirates can classify benign and malignant tissues[J]. Clin Chem 2008;54:1716–24.
[43] Porkka KP, Pfeiffer MJ, Waltering KK, et al.MicroRNA expression profiling in prostate cancer[J]. Cancer Res 2007;67:6130–5.
[44] Ozen M, Creighton CJ, Ozdemir M, Widespread deregulation of microRNA expression in human prostate cancer[J]. Oncogene 2008;27:1788–93.