MiR-195 suppresses non-small cell lung cancer by targeting CHEK1

Oncotarget. 2015 Apr 20;6(11):9445-56. doi: 10.18632/oncotarget.3255.

Abstract

MiR-195 suppresses tumor growth and is associated with better survival outcomes in several malignancies including non-small cell lung cancer (NSCLC). Our previous study showed high miR-195 plasma levels associated with favorable overall survival of non-smoking women with lung adenocarcinoma. To further elucidate role of miR-195 in NSCLC, we conducted in vitro experiment as well as clinical studies in a cohort of 299 NSCLC samples. We demonstrated that miR-195 expression was lower in tumor tissues and was associated with poor survival outcome. Overexpression of miR-195 suppressed tumor cell growth, migration and invasion. We discovered that CHEK1 was a direct target of miR-195, which decreased CHEK1 expression in lung cancer cells. High expression of CHEK1 in lung tumors was associated with poor overall survival. Our results suggest that miR-195 suppresses NSCLC and predicts lung cancer prognosis.

Keywords: CHEK1; cell cycle; miR-195; non-small cell lung cancer; prognosis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adenocarcinoma / chemistry
  • Adenocarcinoma / genetics
  • Adenocarcinoma / mortality
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / chemistry
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Squamous Cell / chemistry
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / mortality
  • Cell Cycle Checkpoints
  • Cell Division
  • Cell Line, Tumor
  • Cell Movement
  • Checkpoint Kinase 1
  • Cyclins / biosynthesis
  • Cyclins / genetics
  • Down-Regulation
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / chemistry
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics*
  • Prognosis
  • Protein Kinases / biosynthesis
  • Protein Kinases / genetics*
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Transfection

Substances

  • 3' Untranslated Regions
  • Cyclins
  • MIRN195 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Small Interfering
  • Protein Kinases
  • CHEK1 protein, human
  • Checkpoint Kinase 1