The circular RNA NT5E promotes non-small cell lung cancer cell growth via sponging microRNA-134

Aging (Albany NY). 2020 Feb 25;12(4):3936-3949. doi: 10.18632/aging.102861. Epub 2020 Feb 25.

Abstract

The current study tested expression and potential function of circular RNA ecto-5'-nucleotidase (circNT5E) in human non-small cell lung cancer (NSCLC). We show that circNT5E levels are significantly elevated in human NSCLC tissues and cells, correlating with downregulation of its potential targets, miR-134, miR-422a and miR-338. In A549 and primary NSCLC cells, circNT5E shRNA inhibited cancer cell growth, proliferation and migration, whiling inducing apoptosis activation. Conversely, ectopic circNT5E overexpression promoted A549 cell progression in vitro. miR-134 is the primary target of circNT5E in lung cancer cells. RNA-Pull down assay in A549 cells confirmed the direct association between biotinylated-miR-134 and circNT6E. miR-134 levels were significantly increased in circNT5E-silenced A549 cells, but reduced with circNT5E overexpression. Forced overexpression of miR-134 mimicked circNT5E shRNA-induced actions, inhibiting NSCLC cell growth and proliferation. In contrast, miR-134 inhibition largely attenuated circNT5E shRNA-induced anti-NSCLC cell activity. Importantly, circNT5E shRNA was ineffective in miR-134-overexpressed A549 cells. Collectively, circNT5E promotes human NSCLC cell progression possibly by sponging miR-134.

Keywords: NSCLC; cancer progression; circNT5E; miR-134.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5'-Nucleotidase / genetics
  • 5'-Nucleotidase / metabolism*
  • Apoptosis / genetics
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Cell Transformation, Neoplastic / genetics
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • RNA, Circular*

Substances

  • GPI-Linked Proteins
  • MIRN134 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • 5'-Nucleotidase
  • NT5E protein, human