Zhang Xiangyang, Nie Yuqiang, Du Yanlei, Cao Jie, Shen Bo, Li Yuyuang
Guangzhou Key Laboratory of Digestive Disease, Department of Gastroenterology, First Municipal People's Hospital of Guangzhou, Guangzhou Medical University, No.1 Panfu Road, Guangzhou, 510180, China.
Tumour Biol. 2012 Oct;33(5):1589-97. doi: 10.1007/s13277-012-0414-3. Epub 2012 May 12.
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.
微小RNA已成为肿瘤发生的关键调节因子。然而，miR-181a是否参与胃癌的发病机制仍不清楚。在本研究中，我们发现miR-181a在人胃癌组织中过表达。miR-181a模拟物的异位表达促进了SGC-7901胃癌细胞的增殖、集落形成、迁移和侵袭，并抑制了其凋亡，而miR-181a抑制剂的异位表达则抑制了SGC-7901细胞的恶性表型。定点诱变和荧光素酶报告基因检测表明，miR-181a通过靶向KLF6的3'-UTR抑制其表达。蛋白质免疫印迹分析进一步表明，当分别将miR-181a模拟物或抑制剂转染到SGC-7901细胞中时，KLF6蛋白显著减少或增加。总之，这些数据表明KLF6基因是miR-181a的直接靶点，并且miR-181a通过抑制肿瘤抑制因子KLF6的表达在胃癌中发挥癌基因作用。
