miR-21在喉鳞癌中的表达及其与PDCD4的相关研究
摘要
【目的】:探讨miR-21及PDCD4在喉鳞癌中的表达情况,及分析miR-21与其靶基因PDCD4在喉鳞癌中的相关研究。
【方法】:(1)应用半定量RT-PCR检测PDCD4在喉鳞癌组织(38例)及癌旁正常组织(38例)中的表达,并结合临床资料分析PDCD4与肿瘤临床病理学特性的相关性。
(2)运用TaqMan? real-time RT-PCR方法检测miR-21在喉鳞癌组织(38例)及癌旁正常组织(38例)中的表达情况。
【结果】:(1)半定量RT-PCR检测结果显示,PDCD4 mRNA在喉鳞癌组织中下调率达86.8%,同癌旁正常组织相比,喉鳞癌组织中PDCD4 mRNA表达明显下调(P<0.05);PDCD4 mRNA表达与肿瘤的分化程度、TNM分期及淋巴转移密切相关(P<0.05),在肿瘤的不同解剖分区中表达无显著差异(P>0.05);在不同分化程度喉鳞癌组织之间PDCD4 mRNA表达存在明显差异,随着分化程度下降,表达明显下调;有淋巴结转移者的PDCD4 mRNA表达显著低于无淋巴结转移者。
(2)配对样本Wilcoxon符号秩检验,发现miR-21的数据有统计学意义(P<0.05), miR-21在喉鳞癌病例样本中明显高表达。
【结论】: miR-21与PDCD4的表达呈负相关性,miR-21与PDCD4在喉鳞癌中的异常表达可能与喉鳞癌的发生、发展有关,miR-21可能抑制PDCD4的表达,减弱PDCD4抑制肿瘤细胞生长的能力,从而促进肿瘤的发生和发展。
【Objective】:To undersand the expression of miR-21 and PDCD4 and discuss their relationships in the laryngeal squamous carcinoma.
【Method】:(1) RT-PCR was used to detect the expression of PDCD4 in the laryngeal squamous carcinoma and adjacent non-cancerous tissues and discussed their associations between PDCD4 and tumor biological characters.
(2) TaqMan? miRNA assays was employed to detect the expression of miR-21 in the laryngeal squamous carcinoma;
【Result】:(1) By RT-PCR test , the down-regulated rate of PDCD4 mRNA in the laryngeal squamous carcinoma were 86.8%(P<0.05). Our study indicated that the expression of PDCD4 has a close relationship with proceeding of the laryngeal squamous carcinoma. Expression of PDCD4 mRNA was highly correlated with tumor differentiation、the TNM stage and lymph node metastasis(P<0.05). On the other hand, its expression was no significant different in the clinical type(P>0.05). In addition, experimental results had convincingly demonstrated that low expression of PDCD4 mRNA was highly associated with decreased tumor differentiation、the TNM stage and lymph node metastasis. while the lower expressions of PDCD4 mRNA in tumor tissues with lymphatica metastasis is higher than these with out lymphatica.
(2) By matched samples Wilcoxon signed-rank test,finding datas of miR-21 had statistic meaning(P<0.05),and the expression of miR-21 was up-regulated which had significantly different in the laryngeal squamous carcinoma.
【Conclusion】:The expressions of miR-21 and PDCD4 mRNA was a significantly Negative correlation in the laryngeal squamous carcinoma. The Abnormal expression of the miR-21 and PDCD4 mRNA might have relationships with the formation of the laryngeal squamous carcinoma. miR-21 might inhibit the expression of PDCD4,to reduce the ability of PDCD4 to inhibit tumor cell growth, thus, contributed to tumorigenesis and development.
【方法】:(1)应用半定量RT-PCR检测PDCD4在喉鳞癌组织(38例)及癌旁正常组织(38例)中的表达,并结合临床资料分析PDCD4与肿瘤临床病理学特性的相关性。
(2)运用TaqMan? real-time RT-PCR方法检测miR-21在喉鳞癌组织(38例)及癌旁正常组织(38例)中的表达情况。
【结果】:(1)半定量RT-PCR检测结果显示,PDCD4 mRNA在喉鳞癌组织中下调率达86.8%,同癌旁正常组织相比,喉鳞癌组织中PDCD4 mRNA表达明显下调(P<0.05);PDCD4 mRNA表达与肿瘤的分化程度、TNM分期及淋巴转移密切相关(P<0.05),在肿瘤的不同解剖分区中表达无显著差异(P>0.05);在不同分化程度喉鳞癌组织之间PDCD4 mRNA表达存在明显差异,随着分化程度下降,表达明显下调;有淋巴结转移者的PDCD4 mRNA表达显著低于无淋巴结转移者。
(2)配对样本Wilcoxon符号秩检验,发现miR-21的数据有统计学意义(P<0.05), miR-21在喉鳞癌病例样本中明显高表达。
【结论】: miR-21与PDCD4的表达呈负相关性,miR-21与PDCD4在喉鳞癌中的异常表达可能与喉鳞癌的发生、发展有关,miR-21可能抑制PDCD4的表达,减弱PDCD4抑制肿瘤细胞生长的能力,从而促进肿瘤的发生和发展。
【Objective】:To undersand the expression of miR-21 and PDCD4 and discuss their relationships in the laryngeal squamous carcinoma.
【Method】:(1) RT-PCR was used to detect the expression of PDCD4 in the laryngeal squamous carcinoma and adjacent non-cancerous tissues and discussed their associations between PDCD4 and tumor biological characters.
(2) TaqMan? miRNA assays was employed to detect the expression of miR-21 in the laryngeal squamous carcinoma;
【Result】:(1) By RT-PCR test , the down-regulated rate of PDCD4 mRNA in the laryngeal squamous carcinoma were 86.8%(P<0.05). Our study indicated that the expression of PDCD4 has a close relationship with proceeding of the laryngeal squamous carcinoma. Expression of PDCD4 mRNA was highly correlated with tumor differentiation、the TNM stage and lymph node metastasis(P<0.05). On the other hand, its expression was no significant different in the clinical type(P>0.05). In addition, experimental results had convincingly demonstrated that low expression of PDCD4 mRNA was highly associated with decreased tumor differentiation、the TNM stage and lymph node metastasis. while the lower expressions of PDCD4 mRNA in tumor tissues with lymphatica metastasis is higher than these with out lymphatica.
(2) By matched samples Wilcoxon signed-rank test,finding datas of miR-21 had statistic meaning(P<0.05),and the expression of miR-21 was up-regulated which had significantly different in the laryngeal squamous carcinoma.
【Conclusion】:The expressions of miR-21 and PDCD4 mRNA was a significantly Negative correlation in the laryngeal squamous carcinoma. The Abnormal expression of the miR-21 and PDCD4 mRNA might have relationships with the formation of the laryngeal squamous carcinoma. miR-21 might inhibit the expression of PDCD4,to reduce the ability of PDCD4 to inhibit tumor cell growth, thus, contributed to tumorigenesis and development.
引文
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[3] Michele Avissar,Brock C. Christensen,Karl T, et al. Marsit MicroRNA Expression Ratio Is Predictive of Head and Neck Squamous Cell Carcinoma. Clin Cancer Res 2009;15(8)
[4] Sevignani C, Calin GA, Nnadi SC, et al. MicroRNA genes are frequently located near mouse cancer susceptibility loci. Proc Natl Acad Sci USA 2007:104: 8017-8022
[5] Haasch D,Chen YW,et al. T-cell activation induces a noncoding RNA transcript sensitive to inhibition by immunosuppressant drugs and encoded by the protooncogene, BIC [J]. Cell Immunol. 2002.217(1):78-86.
[6] Esquela-Kerseher A,Slack FJ. Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer .2006, 6:259-269.
[7] He L, Thomson JM, Hemann MT, Hernando-Monge E, et al. A microRNA polycistron as a potential human oncogene, Nature 2005,434:828-833.
[8] Lu J, Getz G, Miska EA, Alvarez-Saavedra E, et al. MicroRNA expression profiles classify human cancers. Nature 2005, 435:834-838.
[9] Meltzer PS. Cancer genomics: small RNAs with big impacts. Nature 2005,435:745-746.
[10] Takamizawa J, Konishi H, Yanagisawa K, Tomida S, et al. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 2004,64:3753-3756.
[11] Johnson SM, Grosshans H, Shingara J, Byrom M, et al. RAS is regulated by the let-7 microRNA family. Cell 2005,120:635-647.
[12] Iorio MV, Ferracin M, Liu CG, Veronese A, et al. Micro RNA gene expression deregulation in human breast cancer. Cancer Res 2005,65:7065-7070.
[13] Shibahara K, Asano M, Ishida Y, et al. Isolation of a novel mouse gene MA-3 that is induced upon programmed cell death. Gene, 1995,166:297.
[14] Soejima H, Miyoshi O, Yoshinaga H, et al. Assignment of the programmed cell death 4 (PDCD4) to human chromosome band 10q24 by in situ hybridization. Cytogent Cell Gent,1999,87:113.
[15] Yoshinaga H, Matsuhashi S, Ahanek J, et al. Expression and identification of H731 gene product in HeLa cells. Cell Mol Bio,1997,1:121.
[16]孙玮,高飞,张利宁.新的抑癌基因PDCD4最新研究进展.药物分析杂志Chin J Pham Anal 2007,27.
[17] Jansen AP, Camalier CE, et al. Characterization of programmed cell death 4 in multiple human cancers a novel enhancer of drug sensitivity. Mol Cancer Ther, 2004,103.
[18] Hilliard A, Hilliard B, Zheng SJ, et al. Translational regulation of autoimmune inflammation and lymphoma genesis. J Immunol, 2006,177:8095.
[19] Hu H, Li Y, Gu J,et al. Antisense oligonucleotide against miR-21 inhibits migration and induces apoptosis in leukemic K562 cells. Leuk Lymphoma.2010 .2. 8.
[20] Shibahara K, Asano M, Ishida Y, Aoki T, Koike T, et al. Isolation of a novel mouse gene MA-3 that is induced upon programmed cell death,Gene.,1995.,166,297-301.
[21] Goke A, Goke R, Kolle A, et al. DUG is a novel homologue of translation initiation factor 4G that binds e1F4A, Bioehem Biophys Res Commun ,2002,297,78-82.
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