The chromatin modifier MORC2 affects glucose metabolism by regulating the expression of lactate dehydrogenase A through a feed forward loop with c-Myc

FEBS Lett. 2021 May;595(9):1289-1302. doi: 10.1002/1873-3468.14062. Epub 2021 Mar 12.

Abstract

Microrchidia family CW-type zinc finger 2 (MORC2) is a recently identified chromatin modifier with an emerging role in cancer metastasis. However, its role in glucose metabolism, a hallmark of malignancy, remains to be explored. We found that MORC2 is a glucose-inducible gene and a target of c-Myc. Our meta-analysis revealed that MORC2 expression is positively correlated with the expression of enzymes involved in glucose metabolism in breast cancer patients. Furthermore, overexpression of MORC2 in MCF-7 and BT-549 cells augmented the expression and activity of a key glucose metabolism enzyme, lactate dehydrogenase A (LDHA). Conversely, selective knockdown of MORC2 by siRNA markedly decreased LDHA expression and activity and in turn reduced cancer cell migration. Collectively, these findings provide evidence that MORC2, a glucose-inducible gene, modulates the migration of breast cancer cells through the MORC2-c-Myc-LDHA axis.

Keywords: LDHA; MORC2; c-Myc; glucose metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatin / genetics
  • Gene Expression Regulation / genetics
  • Glucose / genetics
  • Humans
  • Lactate Dehydrogenase 5 / genetics*
  • MCF-7 Cells
  • Proto-Oncogene Proteins c-myc / genetics*
  • RNA, Small Interfering / genetics
  • Signal Transduction / genetics
  • Transcription Factors / genetics*

Substances

  • Chromatin
  • MORC2 protein, human
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • RNA, Small Interfering
  • Transcription Factors
  • Lactate Dehydrogenase 5
  • Glucose