MicroRNA-195 controls MICU1 expression and tumor growth in ovarian cancer

Geeta Rao, Shailendra Kumar Dhar Dwivedi, Yushan Zhang, Anindya Dey, Khader Shameer, Ramachandran Karthik, Subramanya Srikantan, Md Nazir Hossen, Jonathan D. Wren, Muniswamy Madesh, Joel T. Dudley, Resham Bhattacharya, Priyabrata Mukherjee

Research output: Contribution to journalArticlepeer-review

Abstract

MICU1 is a mitochondrial inner membrane protein that inhibits mitochondrial calcium entry; elevated MICU1 expression is characteristic of many cancers, including ovarian cancer. MICU1 induces both glycolysis and chemoresistance and is associated with poor clinical outcomes. However, there are currently no available interventions to normalize aberrant MICU1 expression. Here, we demonstrate that microRNA-195-5p (miR-195) directly targets the 3′ UTR of the MICU1 mRNA and represses MICU1 expression. Additionally, miR-195 is under-expressed in ovarian cancer cell lines, and restoring miR-195 expression reestablishes native MICU1 levels and the associated phenotypes. Stable expression of miR-195 in a human xenograft model of ovarian cancer significantly reduces tumor growth, increases tumor doubling times, and enhances overall survival. In conclusion, miR-195 controls MICU1 levels in ovarian cancer and could be exploited to normalize aberrant MICU1 expression, thus reversing both glycolysis and chemoresistance and consequently improving patient outcomes.

Original languageEnglish (US)
Article numbere48483
JournalEMBO Reports
Volume21
Issue number10
DOIs
StatePublished - Oct 5 2020

Keywords

  • MICU1/CBARA1
  • Ovarian cancer
  • chemoresistance
  • glycolysis
  • miR-195

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'MicroRNA-195 controls MICU1 expression and tumor growth in ovarian cancer'. Together they form a unique fingerprint.

Cite this