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

肿瘤抑制因子 miR-486-5p 在非小细胞肺癌中直接抑制致癌基因 CDK4

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

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.

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