title: MiR-613 induces cell cycle arrest by targeting CDK4 in non-small cell lung cancer.
abstract: BACKGROUND
  Deregulation of microRNAs (miRNAs) has been associated with a variety of cancers, including non-small cell lung cancer (NSCLC). Here, we investigated anomalous miR-613 expression and its possible functional consequences in primary NSCLC samples and NSCLC-derived cell lines.
  
  
  METHODS
  The expression of miR-613 was measured by quantitative RT-PCR in 56 primary NSCLC tissues and adjacent non-tumor tissues. The effect of miR-613 up- or down-regulation in NSCLC-derived cells was evaluated in vitro by cell viability and colony formation assays and in vivo by growth assays in xenografted nude mice.
  
  
  RESULTS
  Using quantitative RT-PCR, we found that miR-613 was down-regulated in 76.8 % (43/56) of the primary NSCLC tissues tested when compared to the adjacent non-tumor tissues. We also found that the miR-613 mimic used reduced in vitro cell viability and colony formation by inducing cell cycle arrest in NSCLC-derived cells, and inhibited in vivo tumor cell growth in xenografted nude mice. Inversely, we found that the miR-613 inhibitor used increased the viability and colony forming capacity of NSCLC-derived cells and tumor cell growth in xenografted nude mice. In addition, we identified CDK4 as a potential target of miR-613 using in silico Miranda predictions. Subsequent dual-luciferase reporter assays revealed that CDK4 acts as a direct target of miR-613. Concordantly, we found that both miR-613 mimics and inhibitors could decrease and increase CDK4 protein levels in NSCLC-derived cells, respectively.
  
  
  CONCLUSIONS
  From our results we conclude that miR-613 may act as a tumor suppressor in NSCLC and may serve as a tool for miRNA-based NSCLC therapy.
authors.affiliation: The 2nd Department of Respiratory Disease, The Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan, 646000, China.
authors.forename: Duo
authors.initials: D
authors.lastname: Li
authors.affiliation: The 2nd Department of Respiratory Disease, The Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan, 646000, China.
authors.forename: Dong-Qiong
authors.initials: DQ
authors.lastname: Li
authors.affiliation: Intensive Care Unit, The Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan, 646000, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Thoracic Surgery Department, The Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan, 646000, China. tangxj2014@126.com.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Tang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D059447:Cell Cycle Checkpoints; D049109:Cell Proliferation; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged
chemical_list: C561374:MIRN613 microRNA, human; D035683:MicroRNAs; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4
keywords: CDK4; Cell cycle; Lung cancer; miR-613