Let-7c inhibits A549 cell proliferation through oncogenic TRIB2 related factors

FEBS Lett. 2013 Aug 19;587(16):2675-81. doi: 10.1016/j.febslet.2013.07.004. Epub 2013 Jul 11.

Abstract

MicroRNAs have tumor suppressive or oncogenic roles in carcinogenesis. This study aimed to investigate the mechanism of let-7c in suppressing lung cancer cell proliferation. First, let-7c was revealed to be able to inhibit lung adenocarcinoma cell proliferation significantly. TRIB2 was further demonstrated to be a novel target and negatively regulated by let-7c. As downstream signals of TRIB2, the activities of C/EBP-α and phosphorylated p38MAPK were increased obviously in let-7c-treated cells compared with controls. Our results demonstrate that, through regulating the expression of TRIB2 and its downstream factors, let-7c can effectively inhibit A549 cell proliferation in vitro and in vivo.

Keywords: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; ASO; C/EBP; CCAAT/enhancer-binding protein; Cell proliferation; Gene expression; HCC; Let-7c; Lung adenocarcinoma; MAPK; MTT; TRIB2 gene; antisense oligonucleotides; hepatocellular carcinoma; miRNAs; microRNAs; mitogen-activated protein kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • CCAAT-Enhancer-Binding Protein-alpha / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Proliferation*
  • Gene Expression Regulation, Neoplastic*
  • Genetic Vectors
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Mice
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Neoplasm Transplantation
  • Oligonucleotides, Antisense / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • CCAAT-Enhancer-Binding Protein-alpha
  • Intracellular Signaling Peptides and Proteins
  • MicroRNAs
  • Oligonucleotides, Antisense
  • mirnlet7 microRNA, human
  • Green Fluorescent Proteins
  • Calcium-Calmodulin-Dependent Protein Kinases
  • TRIB2 protein, human
  • p38 Mitogen-Activated Protein Kinases