TY - JOUR
T1 - MicroRNA-195 controls MICU1 expression and tumor growth in ovarian cancer
AU - Rao, Geeta
AU - Dwivedi, Shailendra Kumar Dhar
AU - Zhang, Yushan
AU - Dey, Anindya
AU - Shameer, Khader
AU - Karthik, Ramachandran
AU - Srikantan, Subramanya
AU - Hossen, Md Nazir
AU - Wren, Jonathan D.
AU - Madesh, Muniswamy
AU - Dudley, Joel T.
AU - Bhattacharya, Resham
AU - Mukherjee, Priyabrata
N1 - Publisher Copyright:
© 2020 The Authors
PY - 2020/10/5
Y1 - 2020/10/5
N2 - 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.
AB - 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.
KW - MICU1/CBARA1
KW - Ovarian cancer
KW - chemoresistance
KW - glycolysis
KW - miR-195
UR - http://www.scopus.com/inward/record.url?scp=85089863689&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85089863689&partnerID=8YFLogxK
U2 - 10.15252/embr.201948483
DO - 10.15252/embr.201948483
M3 - Article
C2 - 32851774
AN - SCOPUS:85089863689
SN - 1469-221X
VL - 21
JO - EMBO Reports
JF - EMBO Reports
IS - 10
M1 - e48483
ER -