DOI: 10.1101/476812Nov 22, 2018Paper

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

BioRxiv : the Preprint Server for Biology
Paresh Kumar PurohitNeeru Saini

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. Which 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 ...Continue Reading

Related Concepts

Malignant Neoplasms
Diagnostic Imaging
Mitochondria
Superoxide Dismutase
Free Radical Scavengers
Apoptosis
Reactive Oxygen Species
Mitochondrial Fission
Oxidative Stress
Research Study

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