Yang Feng-Qiang, Wang Ji-Jiao, Yan Jia-Sheng, Huang Jian-Hua, Li Wei, Che Jian-Ping, Wang Guang-Chun, Liu Min, Zheng Jun-Hua
Department of Urology, Shanghai Tenth People's Hospital, Tongji University Shanghai, 200072, China.
Department of Endocrinology, The Second Hospital Affiliated to Dalian Medical University Dalian, 116027, China.
Int J Clin Exp Med. 2014 Oct 15;7(10):3289-96. eCollection 2014.
Accumulating evidence suggests that metformin, a biguanide class of anti-diabetic drugs, possesses anti-cancer properties and may reduce cancer risk and improve prognosis. However, the mechanism by which metformin affects various cancers, including renal cancer still unknown. MiR-26a induces cell growth, cell cycle and cell apoptosis progression via direct targeting of Bcl-2, clyclin D1 and PTEN in cancer cells. In the present study, we used 786-O human renal cancer cell lines to study the effects and mechanisms of metformin. Metformin treatment inhibited RCC cells proliferation by increasing expression of miR-26a in 786-O cells (P < 0.05). As a result, protein abundance of Bcl-2 and cyclin D1 was decreased and PTEN was increased in cells exposed to metformin. Also over-expression of miR-26a can inhibited cell proliferation by down-regulating Bcl-2, cyclin D1 and up-regulating PTEN expression. Therefore, these data for the first time provide novel evidence for a mechanism that the anticancer activities of metformin are due to upregulation of miR-26a and affect its downstream target gene.
越来越多的证据表明，二甲双胍这种双胍类抗糖尿病药物具有抗癌特性，可能降低癌症风险并改善预后。然而，二甲双胍影响包括肾癌在内的各种癌症的机制仍不清楚。MiR-26a通过直接靶向癌细胞中的Bcl-2、细胞周期蛋白D1和PTEN来诱导细胞生长、细胞周期和细胞凋亡进程。在本研究中，我们使用786-O人肾癌细胞系来研究二甲双胍的作用及其机制。二甲双胍处理通过增加786-O细胞中miR-26a的表达来抑制肾癌细胞的增殖（P < 0.05）。结果，在暴露于二甲双胍的细胞中，Bcl-2和细胞周期蛋白D1的蛋白丰度降低，PTEN增加。此外，miR-26a的过表达可通过下调Bcl-2、细胞周期蛋白D1和上调PTEN表达来抑制细胞增殖。因此，这些数据首次为二甲双胍的抗癌活性归因于miR-26a的上调并影响其下游靶基因这一机制提供了新证据。
