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miRNA-10a在胃癌中的功能及其甲基化调控
  • 分类:R735.2[医药卫生—肿瘤;医药卫生—临床医学]
  • 作者机构:[1]山西医科大学外科学,山西太原030032, [2]北京大学第九临床医学院北京世纪坛医院检验中心,北京100038, [3]中国医学科学院基础医学研究所北京协和医学院基础学院,北京100005, [4]山西大医院外科学,山西太原030032
  • 相关基金:国家自然科学基金(91129716).
中文摘要:

目的研究miRNA-10a在胃癌中的表达及其在胃癌中的功能,探讨其启动子区的高甲基化与胃癌发生的相关性。方法使用Taqman探针对35对胃癌组织标本进行实时定量PCR检测,统计学分析miRNA-10a的表达情况与临床病理因素的相关性,随后使用甲基化特异性PCR(MSP)检测样本中miRNA-10a上游启动子区的甲基化情况。并通过细胞增殖实验研究miRNA-10a在胃癌细胞系中的功能。结果在35对胃癌样本中,其中.24例miRNA-10a的表达水平下调。11例表达水平上调。与临床病理因素的相关性分析显示,miRNA-10a在胃癌组织中的低表达,与胃癌的TNM分期呈负相关(P〈0.05)。MSP结果显示,癌组织的甲基化水平明显高于相对应的癌旁组织,差异有统计学意义(P〈0.05)。细胞增殖实验显示,过表达miRNA-10a后能够明显抑制胃癌细胞的增殖速度。结论胃癌组织中miRNA-10a的表达呈现普遍的低表达趋势,且miRNA-10a的低表达与胃癌的TNM分期呈负相关,其启动子区的高甲基化可能是导致miRNA-10a表达下调,参与胃癌发生的原因之一,并且miRNA-10a可能在胃癌的发生中起肿瘤抑制基因的作用。

英文摘要:

Objective To investigate the expression of miRNA-10a and its function in gastric cancer (GC) and also its genomic promoter DNA methylation. Methods Detected the expression of miRNA-10a in 35 GC patients by real-time i?CR using Taqrnan probes.The association between miRNA-10a expression and clinicopathological factors was ana- lyzed by SPSS 19.0.DNA methylation status was detected by methylation-specific PCR (MSP).The function of miRNA- i0a on cell proliferation was detected by CCK-8 kit. Results Out of 35 GC patients,the expression of miRNA-10a was down-regulated in 24 cases compared with the adjacent tissues.The low expression of miRNA-10a was signifi- cantly associated with gastric cancer TNM stage (P 〈 0.05).The methylation level in GC tissues was higher than in the matched adjacent non-neoplastic tissues (P 〈 0.05).Overexpression of miRNA-10a reduced the cell proliferation of GC cell lines. Conclusion miRNA-10a is down-regulated in majority of GC tissues possibly because of the high methyla- tion level of its promoter in GC tissues.The inhibition of miRNA-10a on cell proliferation suggested that it acted as a tumor suppressor in gastric cancer.

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