title: Direct repression of the oncogene CDK4 by the tumor suppressor miR-486-5p in non-small cell lung cancer.
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.
authors.affiliation: School of Life Sciences, Shanghai University, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shao
authors.affiliation: School of Life Sciences, Shanghai University, Shanghai, China.
authors.forename: Yu-Qing
authors.initials: YQ
authors.lastname: Shen
authors.affiliation: School of Life Sciences, Shanghai University, Shanghai, China.
authors.forename: Yan-Li
authors.initials: YL
authors.lastname: Li
authors.affiliation: School of Life Sciences, Shanghai University, Shanghai, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Liang
authors.affiliation: School of Life Sciences, Shanghai University, Shanghai, China.
authors.forename: Bing-Jie
authors.initials: BJ
authors.lastname: Zhang
authors.affiliation: Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Sheng-Di
authors.initials: SD
authors.lastname: Lu
authors.affiliation: School of Life Sciences, Shanghai University, Shanghai, China.|Experimental Center for Life Sciences, Shanghai University, Shanghai, China.
authors.forename: Yan-Yun
authors.initials: YY
authors.lastname: He
authors.affiliation: School of Life Sciences, Shanghai University, Shanghai, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Central Laboratory, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Qiang-Ling
authors.initials: QL
authors.lastname: Sun
authors.affiliation: School of Life Sciences, Shanghai University, Shanghai, China.
authors.forename: You-Xin
authors.initials: YX
authors.lastname: Jin
authors.affiliation: School of Life Sciences, Shanghai University, Shanghai, China.
authors.forename: Zhong-Liang
authors.initials: ZL
authors.lastname: Ma
mesh_terms: D000072283:A549 Cells; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D059585:G1 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: C560945:MIRN486 microRNA, human; D035683:MicroRNAs; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4
keywords: CDK4; NSCLC; cell cycle; methylation; miR-486-5p