Autotaxin is a novel target of microRNA-101-3p

FEBS Open Bio. 2019 Mar 1;9(4):707-716. doi: 10.1002/2211-5463.12608. eCollection 2019 Apr.

Abstract

Autotaxin (ATX), a vital enzyme that generates lysophosphatidic acid (LPA), affects many biological processes, including tumorigenesis, via the ATX-LPA axis. In this study, we demonstrate that microRNA-101-3p (miR-101-3p), a well-known tumor suppressor, downregulates ATX expression at the posttranscriptional level. We found that miR-101-3p inhibits ATX regulation by directly targeting a conserved sequence in the ATX mRNA 3'UTR. Moreover, we observed an inverse correlation between ATX and miR-101-3p levels in various types of cancer cells. ATX is highly expressed in several human cancers. Here, we verified that ATX expression is significantly inhibited by miR-101-3p in U87 and HCT116 cells. ATX downregulation contributed to the suppression of migration, invasion, and proliferation mediated by miR-101-3p; furthermore, the tumor-suppressing activity of miR-101-3p was partially reduced by the addition of LPA in U87 cells. Our data suggest that ATX is a novel target of miR-101-3p.

Keywords: autotaxin; cancer cell; invasion; miR‐101‐3p; migration; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic*
  • HCT116 Cells
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Phosphoric Diester Hydrolases / genetics*
  • Phosphoric Diester Hydrolases / metabolism
  • Signal Transduction / genetics

Substances

  • MIRN101 microRNA, human
  • MicroRNAs
  • Phosphoric Diester Hydrolases
  • alkylglycerophosphoethanolamine phosphodiesterase