MicroRNA-195 controlsMICU1 expression and tumor growth in ovarian cancer

MICU1 is a mitochondrial inner membrane protein that inhibits mitochondrial calcium entry; elevatedMICU1 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 aberrantMICU1 expression. Here, we demonstrate that microRNA-195-5p (miR-195) directly targets the 3 ' UTRof theMICU1mRNAand repressesMICU1 expression. Additionally, miR-195 is under-expressed in ovarian cancer cell lines, and restoring miR-195 expression reestablishes nativeMICU1 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 controlsMICU1 levels in ovarian cancer and could be exploited to normalize aberrantMICU1 expression, thus reversing both glycolysis and chemoresistance and consequently improving patient outcomes.