The epigenetically-regulated miR-34a targeting c-SRC suppresses RAF/MEK/ERK signaling pathway in K-562 cells

Leuk Res. 2017 Apr:55:91-96. doi: 10.1016/j.leukres.2017.01.020. Epub 2017 Jan 22.

Abstract

Previous reports show that miR-34a suppressed K-562 cell proliferation and contributed to megakaryocytic differentiation of K-562 cells. Here, we reported that miR-34a, a tumor suppressor gene, is down-regulated in the K-562 cells and chronic myeloid leukemia (CML) patients due to aberrant DNA hypermethylation. c-SRC is a target of miR-34a. Restoring miR-34a expression resulted in down-regulation of c-SRC and phosphorylated (Tyr416) c-SRC protein in K-562 cells, which consequently triggered suppression of the RAF/MEK/ERK signaling pathway to decrease cell proliferation.

Keywords: Epigenetic; Methylation; c-SRC; miR-34a.

MeSH terms

  • CSK Tyrosine-Protein Kinase
  • Cell Proliferation
  • DNA Methylation
  • Epigenesis, Genetic / physiology*
  • Gene Expression Regulation
  • Humans
  • K562 Cells
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • MAP Kinase Signaling System / drug effects*
  • MicroRNAs / physiology*
  • Phosphorylation
  • raf Kinases / metabolism*
  • src-Family Kinases / antagonists & inhibitors*
  • src-Family Kinases / metabolism

Substances

  • MIRN34 microRNA, human
  • MicroRNAs
  • CSK Tyrosine-Protein Kinase
  • src-Family Kinases
  • CSK protein, human
  • raf Kinases