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

EMBO Rep. 2020 Oct 5;21(10):e48483. doi: 10.15252/embr.201948483. Epub 2020 Aug 27.


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.

Keywords: MICU1/CBARA1; Ovarian cancer; chemoresistance; glycolysis; miR-195.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Cation Transport Proteins* / genetics
  • Cation Transport Proteins* / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glycolysis / genetics
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Mitochondrial Membrane Transport Proteins / metabolism
  • Ovarian Neoplasms* / genetics


  • Calcium-Binding Proteins
  • Cation Transport Proteins
  • MICU1 protein, human
  • MIRN195 microRNA, human
  • MicroRNAs
  • Mitochondrial Membrane Transport Proteins