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Micro RNA ‐195 controls MICU 1 expression and tumor growth in ovarian cancer
Author(s) -
Rao Geeta,
Dwivedi Shailendra Kumar Dhar,
Zhang Yushan,
Dey Anindya,
Shameer Khader,
Karthik Ramachandran,
Srikantan Subramanya,
Hossen Md Nazir,
Wren Jonathan D,
Madesh Muniswamy,
Dudley Joel T,
Bhattacharya Resham,
Mukherjee Priyabrata
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201948483
Subject(s) - library science , medicine , gerontology , family medicine , computer science
MICU 1 is a mitochondrial inner membrane protein that inhibits mitochondrial calcium entry; elevated MICU 1 expression is characteristic of many cancers, including ovarian cancer. MICU 1 induces both glycolysis and chemoresistance and is associated with poor clinical outcomes. However, there are currently no available interventions to normalize aberrant MICU 1 expression. Here, we demonstrate that micro RNA ‐195‐5p (miR‐195) directly targets the 3′ UTR of the MICU 1 mRNA and represses MICU 1 expression. Additionally, miR‐195 is under‐expressed in ovarian cancer cell lines, and restoring miR‐195 expression reestablishes native MICU 1 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 MICU 1 levels in ovarian cancer and could be exploited to normalize aberrant MICU 1 expression, thus reversing both glycolysis and chemoresistance and consequently improving patient outcomes.