The MicroRNA-551a/MEF2C Axis Regulates the Survival and Sphere Formation of Cancer Cells in Response to 5-Fluorouracil

Mol Cells. 2019 Feb 28;42(2):175-182. doi: 10.14348/molcells.2018.0288. Epub 2019 Jan 24.

Abstract

microRNAs regulate a diverse spectrum of cancer biology, including tumorigenesis, metastasis, stemness, and drug resistance. To investigate miRNA-mediated regulation of drug resistance, we characterized the resistant cell lines to 5-fluorouracil by inducing stable expression of miRNAs using lenti-miRNA library. Here, we demonstrate miR-551a as a novel factor regulating cell survival after 5-FU treatment. miR-551a-expressing cells (Hep3B-lenti-miR-551a) were resistant to 5-FU-induced cell death, and after 5-FU treatment, and showed significant increases in cell viability, cell survival, and sphere formation. It was further shown that myocyte-specific factor 2C is the direct target of miR-551a. Our results suggest that miR-551a plays a novel function in regulating 5-FU-induced cell death, and targeting miR-551a might be helpful to sensitize cells to anti-cancer drugs.

Keywords: anti-cancer drug resistance; cell survival; hepatocellular carcinoma; microRNA; sphere formation.

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Base Sequence
  • Cell Survival / drug effects
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics
  • Fluorouracil / pharmacology*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • MEF2 Transcription Factors / genetics
  • MEF2 Transcription Factors / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Spheroids, Cellular / metabolism*
  • Spheroids, Cellular / pathology*
  • Tumor Cells, Cultured

Substances

  • Antimetabolites, Antineoplastic
  • MEF2 Transcription Factors
  • MEF2C protein, human
  • MIRN661 microRNA, human
  • MicroRNAs
  • Fluorouracil