MicroRNA-181a promotes gastric cancer by negatively regulating tumor suppressor KLF6
MicroRNA-181a promotes gastric cancer by negatively regulating tumor suppressor KLF6
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DOI：
10.1007/s13277-012-0414-3
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发表时间：
2012-10-01
期刊：
影响因子：
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通讯作者：
Li, Yuyuang
中科院分区：
文献类型：
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作者：
Zhang, Xiangyang;Nie, Yuqiang;Li, Yuyuang
microRNA已成为肿瘤发生的关键调节因子。然而，miR-181 a是否参与胃癌的发病机制仍不清楚。本研究发现miR-181 a在人胃癌组织中过表达。miR-181 a模拟物的异位表达促进了SGC-7901细胞的增殖、集落形成、迁移和侵袭，抑制了细胞凋亡，而miR-181 a抑制剂的异位表达则抑制了SGC-7901细胞的恶性表型。定点突变和荧光素酶报告基因分析表明miR-181 a通过靶向KLF 6的3 '-UTR抑制KLF 6的表达。Western blot结果显示，miR-181 a模拟物和miR-181 a抑制剂分别转染SGC-7901细胞后，KLF 6蛋白表达明显降低或升高。综上所述，这些数据表明，KLF 6基因是miR-181 a的直接靶点，miR-181 a通过抑制肿瘤抑制因子KLF 6的表达而在胃癌中发挥癌细胞的作用。
MicroRNAs have emerged as crucial regulators of tumorigenesis. However, it remains unknown whether miR-181a is involved in the pathogenesis of gastric cancer. In this study, we found that miR-181a is overexpressed in human gastric cancer tissues. Ectopic expression of miR-181a mimic promoted the proliferation, colony formation, migration, and invasion and inhibited the apoptosis of SGC-7901 gastric cancer cells, whereas ectopic expression of miR-181a inhibitor inhibited the malignant phenotypes of SGC-7901 cells. Site-directed mutagenesis and luciferase reporter assay demonstrated that miR-181a repressed KLF6 expression by targeting its 3'-UTR. Western blot analysis further showed that KLF6 protein was significantly decreased or increased when miR-181a mimic or inhibitor was transfected into SGC-7901 cells, respectively. In summary, these data suggest that KLF6 gene is a direct target of miR-181a and miR-181a functions as an oncomir in gastric cancer by repressing the expression of tumor suppressor KLF6.