title: Downregulation of miR-25 modulates non-small cell lung cancer cells by targeting CDC42.
abstract: The current study aims to investigate the fuctional role of miRNA-25 in non-small cell lung cancer (NSCLC) cells. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-25 in NSCLC cell lines and 11 pairs of human NSCLC and non-cancerous tissues. The inhibitor of miR-25 was stably transfected into NSCLC cell line A549 cells. Then the effects of downregulating miR-25 on cancer cell proliferation, cell cycle arrest, chemosensitivity to cisplatin, and growth of in vivo xenograft were investigated. Direct regulation of miR-25 on its target gene, cell division cycle 42 (CDC42), was examined by luciferase reporter assay, qRT-PCR and western blot. CDC42 was then upregulated in A549 cells to investigate its effect on miR-25-mediated NSCLC cell proliferation and cell cycle arrest. The expression of miR-25 in NSCLC cells or human tissues was significantly higher than that in normal lung cells or adjacent non-cancerous tissues, respectively. Downregulation of miR-25 markedly inhibited A549 cell proliferation, induced G1 cell cycle arrest, increased cisplatin sensitivity, and suppressed the growth of caner cell xenograft in vivo. CDC42 was confirmed to be the directly regulated by miR-25 in A549 cells. Upregulation of CDC42 in A549 cells rescued the inhibitory effect on proliferation and the G1 cell cycle arrest induced by miR-25 downregulation. Our study demonstrates miR-25, by targeting CDC42, is an important regulator in NSCLC.
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Yang
authors.forename: Tianjun
authors.initials: T
authors.lastname: Chen
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.forename: Shuo
authors.initials: S
authors.lastname: Zhang
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.forename: Mingwei
authors.initials: M
authors.lastname: Chen
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology; D015536:Down-Regulation; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D065636:Myotonin-Protein Kinase / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C543351:MIRN25 microRNA, human; D035683:MicroRNAs; C105518:CDC42BPA protein, human; D065636:Myotonin-Protein Kinase; D002945:Cisplatin