Direct repression of the oncogene CDK4 by the tumor suppressor miR-486-5p in non-small cell lung cancer

作者：Shao, Yang; Shen, Yu-Qing; Li, Yan-Li; Liang, Chen; Zhang, Bing-Jie; Lu, Sheng-Di; He, Yan-Yun; Wang, Ping; Sun, Qiang-Ling^*; Jin, You-Xin^*; Ma, Zhong-Liang^*

来源：Oncotarget, 2016, 7(23): 34011-34021.

DOI：10.18632/oncotarget.8514

• miR-486-5p
• CDK4
• NSCLC
• methylation
• cell cycle

MicroRNAs are a class of non-coding single-stranded RNA, 20-23 nucleotide in length, which can be involved in the regulation of gene expression. Through binding with 3'-untranslated regions (3'-UTR), microRNAs can cause degradation of target mRNAs or inhibition of translation, and thus regulating the expression of genes at the post-transcriptional level. In this study, we found that miR-486-5p was significantly downregulated in non-small cell lung cancer (NSCLC) tissues and cell lines, suggesting that miR-486-5p might function as a tumor suppressor in lung cancer. Additionally, we showed that CDK4, an oncogene that plays an important role in cell cycle G1/S phase progression, was directly targeted by miR-486-5p. Furthermore, our data reveals that knockdown of CDK4 by siRNA can inhibit cell proliferation, promote apoptosis, and impede cell-cycle progression. In epigenetics, the upstream promoter of miR-486-5p was strongly regulated by methylation in NSCLC. Collectively, our results suggest that miR-486-5p could not only inhibit NSCLC by downregulating the expression of CDK4, but also be as a promising and potent therapy in the near future.

• 出版日期2016-6-7
• 单位上海交通大学; 上海大学