MicroRNA-135a acts as a putative tumor suppressor by directly targeting very low density lipoprotein receptor in human gallbladder cancer

Cancer Sci. 2014 Aug;105(8):956-65. doi: 10.1111/cas.12463.

Abstract

The precise functions and mechanisms of microRNAs (miR) in gallbladder cancer (GBC) remain elusive. In this study, we found that miR-135a-5p expression is often dampened and correlated with neoplasm histologic grade in GBC. MicroRNA-135a-5p introduction clearly inhibited GBC cell proliferation in vitro and in vivo. Moreover, very low density lipoprotein receptor (VLDLR), which is often upregulated in GBC tissues, was identified as a direct functional target of miR-135a-5p. Furthermore, the p38 MAPK pathway was proven to be involved in miR-135a-VLDLR downstream signaling. Together, these results suggested that the miR-135a-VLDLR-p38 axis may contribute to GBC cell proliferation.

Keywords: Gallbladder cancer; MiR-135a; p38; proliferation; very low density lipoprotein receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blotting, Western
  • Female
  • Gallbladder Neoplasms / genetics*
  • Gallbladder Neoplasms / metabolism*
  • Gene Expression Regulation, Neoplastic / physiology*
  • Genes, Tumor Suppressor
  • Humans
  • MAP Kinase Signaling System / physiology
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Real-Time Polymerase Chain Reaction
  • Receptors, LDL / biosynthesis*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection

Substances

  • MIRN135 microRNA, human
  • MicroRNAs
  • Receptors, LDL
  • VLDL receptor