miR-149 contributes to resistance of 5-FU in gastric cancer via targeting TREM2 and regulating β-catenin pathway

Biochem Biophys Res Commun. 2020 Nov 12;532(3):329-335. doi: 10.1016/j.bbrc.2020.05.135. Epub 2020 Sep 22.

Abstract

Drug resistance remains the unresolved obstacle for gastric cancer (GC) treatment. Recently more and more studies have shown that microRNAs are involved in cancer resistance and could apply to drug resistance therapy in tumors. The relationship between miR-149 and 5-fluorouracil (5-FU) resistance in GC remains unclear. Here we detected miR-149 expression in 5-FU resistance tumor tissues and cell lines, and found that miR-149 expression is upregulated in AGS/5-FU cells compared with AGS cells. Further experiments indicated that overexpression of miR-149 can alleviate 5-FU-induced apoptosis and proliferation inhibition by targeting TREM2. It was also confirmed that TREM2 regulated 5-FU resistance through β-catenin pathway. Generally speaking, our results indicated that miR-149 contributes to resistance of 5-FU in gastric cancer via targeting TREM2 and regulating β-catenin pathway.

Keywords: 5-FU; Drug resistance; Gastric cancer; miR-149.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Fluorouracil / pharmacology*
  • Heterografts
  • Humans
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • RNA, Small Interfering / genetics
  • Receptors, Immunologic / antagonists & inhibitors
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Signal Transduction
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Up-Regulation
  • beta Catenin / antagonists & inhibitors
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • Antineoplastic Agents
  • CTNNB1 protein, human
  • MIRN149 microRNA, human
  • Membrane Glycoproteins
  • MicroRNAs
  • RNA, Small Interfering
  • Receptors, Immunologic
  • TREM2 protein, human
  • beta Catenin
  • Fluorouracil