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

// Yang Shao 1, * , Yu-Qing Shen 1, * , Yan-Li Li 1, * , Chen Liang 1 , Bing-Jie Zhang 1 , Sheng-Di Lu 2 , Yan-Yun He 1, 4 , Ping Wang 1 , Qiang-Ling Sun 3 , You-Xin Jin 1 , Zhong-Liang Ma 1 1 School of Life Sciences, Shanghai University, Shanghai, China 2 Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China 3 Central Laboratory, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China 4 Experimental Center for Life Sciences, Shanghai University, Shanghai, China * These authors have contributed equally to this work Correspondence to: Qiang-Ling Sun, e-mail: shqling@163.com You-Xin Jin, e-mail: jinyouxin@shu.edu.cn Zhong-Liang Ma, e-mail: zlma@shu.edu.cn Keywords: miR-486-5p, CDK4, NSCLC, methylation, cell cycle Received: October 11, 2015 Accepted: March 17, 2016 Published: March 31, 2016 ABSTRACT 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.