MiR-501-3p functions as a tumor suppressor in non-small cell lung cancer by downregulating RAP1A

Exp Cell Res. 2020 Feb 1;387(1):111752. doi: 10.1016/j.yexcr.2019.111752. Epub 2019 Dec 2.

Abstract

MicroRNA-501-3p (miR-501-3p) has been reported to play tumor-suppressive roles in different cancers; however, its expression pattern and biological function in non-small cell lung cancer (NSCLC) remain unknown. In this study, we noted downregulation of miR-501-3p in NSCLC tissues and cell lines. Functional assays showed that overexpression of miR-501-3p suppressed NSCLC cell proliferation, clonogenicity, migration, and invasion. Moreover, miR-501-3p overexpression attenuated in vivo tumor growth in a nude mouse model. In terms of the mechanism, RAP1A was identified as a novel target of miR-501-3p. Overexpression of RAP1A strongly attenuated the inhibitory effects of miR-501-3p on the capacity of NSCLC cells for proliferation and motility. In the clinical samples of NSCLC, miR-501-3p levels negatively correlated with RAP1A expression, which was upregulated in NSCLC. Collectively, these results indicate that miR-501-3p acts as a tumor suppressor in NSCLC by directly targeting RAP1A mRNA and may serve as a theranostic biomarker for patients with NSCLC.

Keywords: Invasion; Non-small cell lung cancer; Proliferation; RAP1A; miR-501-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Down-Regulation / genetics*
  • Gene Expression Regulation, Neoplastic / genetics
  • Genes, Tumor Suppressor / physiology
  • HEK293 Cells
  • Humans
  • Lung Neoplasms / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Up-Regulation / genetics
  • rap1 GTP-Binding Proteins / genetics*

Substances

  • MIRN501 microRNA, human
  • MicroRNAs
  • RAP1A protein, human
  • rap1 GTP-Binding Proteins