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MiR-195 regulates mitochondrial function by targeting mitofusin-2 in breast cancer cells.

ABSTRACT: Mitochondrial dynamics is a highly dysregulated process in cancer. Apoptosis and mitochondrial fission are two concurrent events wherein increased mitochondrial fragmentation serves as a hallmark of apoptosis. We have shown earlier that miR-195 exerts pro-apoptotic effects in breast cancer cells. Herein, we have demonstrated miR-195 as a modulator of mitochondrial dynamics and function. Imaging experiments upon miR-195 treatment have shown that mitochondria undergo extensive fission. We validated mitofusin2 as a potential target of miR-195. This may provide a molecular explanation for the respiratory defects induced by miR-195 over-expression in breast cancer cells. Active, but not total, mitochondrial mass, was reduced with increasing levels of miR-195. We have further shown that miR-195 enhances mitochondrial SOD-2 expression but does not affect PINK1 levels in breast cancer cells. Collectively, we have revealed that miR-195 is a modulator of mitochondrial dynamics by targeting MFN2 thereby impairing mitochondrial function. Concomitantly, it enhances the scavenger of reactive oxygen species (SOD-2) to maintain moderate levels of oxidative stress. Our findings suggest a therapeutic potential of miR-195 in both ER-positive as well as ER-negative breast cancer cells.

SUBMITTER: Purohit PK

PROVIDER: S-EPMC6546347 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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MiR-195 regulates mitochondrial function by targeting mitofusin-2 in breast cancer cells.

Purohit Paresh Kumar PK Edwards Ruairidh R Tokatlidis Kostas K Saini Neeru N

RNA biology 20190425 7

Mitochondrial dynamics is a highly dysregulated process in cancer. Apoptosis and mitochondrial fission are two concurrent events wherein increased mitochondrial fragmentation serves as a hallmark of apoptosis. We have shown earlier that miR-195 exerts pro-apoptotic effects in breast cancer cells. Herein, we have demonstrated miR-195 as a modulator of mitochondrial dynamics and function. Imaging experiments upon miR-195 treatment have shown that mitochondria undergo extensive fission. We validate ...[more]

PMID: 30932749

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MiR-195 regulates mitochondrial function by targeting mitofusin-2 in breast cancer cells.

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MiR-195 regulates mitochondrial function by targeting mitofusin-2 in breast cancer cells.

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