Novel Insights into the Role of Chromatin Remodeler MORC2 in Cancer

Biomolecules. 2023 Oct 15;13(10):1527. doi: 10.3390/biom13101527.

Abstract

A newly discovered chromatin remodeler, MORC2, is a Microrchidia (MORC) family member. MORC2 acts as a chromatin remodeler by binding to the DNA and changing chromatin conformation using its ATPase domain. MORC2 is highly expressed in a variety of human cancers. It controls diverse signaling pathways essential for cancer development through its target genes and interacting partners. MORC2 promotes cancer cells' growth, invasion, and migration by regulating the expression of genes involved in these processes. MORC2 is localized primarily in the nucleus and is also found in the cytoplasm. In the cytoplasm, MORC2 interacts with adenosine triphosphate (ATP)-citrate lyase (ACLY) to promote lipogenesis and cholesterogenesis in cancer. In the nucleus, MORC2 interacts with the transcription factor c-Myc to control the transcription of genes involved in glucose metabolism to drive cancer cell migration and invasion. Furthermore, MORC2 recruits on to the promoters of tumor suppressor genes to repress their transcription and expression to promote oncogenesis. In addition to its crucial function in oncogenesis, it plays a vital role in DNA repair. Overall, this review concisely summarizes the current knowledge about MORC2-regulated molecular pathways involved in cancer.

Keywords: MORC2; cancer invasion and migration; chromatin remodeling; metabolism; post-translational modifications; transcription of genes.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinogenesis
  • Chromatin* / genetics
  • DNA Repair
  • Humans
  • Neoplasms* / genetics
  • Transcription Factors / metabolism

Substances

  • Chromatin
  • Transcription Factors
  • MORC2 protein, human

Grants and funding

S.B.P. is thankful to the Institute of Eminence (IoE), University of Hyderabad, India, for financial support (UoH-IoE-RC5-22-043). N.C. is grateful to IISER Tirupati for the financial support. K.S. thank the University of Zululand for the grant (P419) and appointment as a visiting fellow (to S.B.P.).