Tanshinone ⅡA inhibits human esophageal cancer cell growth through miR-122-mediated PKM2 down-regulation

Arch Biochem Biophys. 2016 May 15:598:50-6. doi: 10.1016/j.abb.2016.03.031. Epub 2016 Mar 31.

Abstract

Pyruvate kinase M2 (PKM2) plays a pivotal role in the growth, survival and metabolic reprogramming of cancer cells. Here, we presented for the first time that tanshinone ⅡA inhibited human esophagus cancer cell growth through miR-122-mediated PKM2 down-regulation pathway. Tanshinone ⅡA inhibited cell proliferation and induced cell cycle arrest in S phase in human Ec109 cells. As expected, tanshinone ⅡA down-regulated PKM2 mRNA and protein expression in Ec109 cells. Given these findings, we further investigated microRNAs regulation of PKM2 and confirmed miR-122 for targeting PKM2. Moreover, we found that tanshinone ⅡA-induced up-regulation of miR-122 expression inhibited PKM2 expression in Ec109 cells. Meanwhile, tanshinone ⅡA inhibited proliferation through miR122-medated PKM2 down-regulation. It was demonstrated that the anticancer activity of tanshinone ⅡA was targeted at metabolic regulation of miR-122/PKM2 in human esophagus cancer cells. Taken together, our results revealed tanshinone ⅡA targeting at PKM2-mediated metabolic reprogramming play an important role in inhibition of esophageal cancer cell growth.

Keywords: Metabolic reprogramming; PKM2; Tanshinone ⅡA; miR-122.

MeSH terms

  • Abietanes / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects*
  • Down-Regulation / drug effects*
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • HeLa Cells
  • Humans
  • MicroRNAs / biosynthesis*
  • Neoplasm Proteins / biosynthesis*
  • Pyruvate Kinase / biosynthesis*
  • RNA, Neoplasm / biosynthesis*

Substances

  • Abietanes
  • Antineoplastic Agents
  • MIRN122 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Neoplasm
  • tanshinone
  • Pyruvate Kinase