Downregulation of the mitochondrial calcium uniporter by cancer-related miR-25.

Current biology : CB 2013 Jan 07

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The recently discovered mitochondrial calcium uniporter (MCU) promotes Ca(2+) accumulation into the mitochondrial matrix. We identified in silico miR-25 as a cancer-related MCU-targeting microRNA family and demonstrate that its overexpression in HeLa cells drastically reduces MCU levels and mitochondrial Ca(2+) uptake, while leaving other mitochondrial parameters and cytosolic Ca(2+) signals unaffected. In human colon cancers and cancer-derived cells, miR-25 is overexpressed and MCU accordingly silenced. miR-25-dependent reduction of mitochondrial Ca(2+) uptake correlates with resistance to apoptotic challenges and can be reversed by anti-miR-25 overexpression. Overall, the data demonstrate that microRNA targeting of mitochondrial Ca(2+) signaling favors cancer cell survival, thus providing mechanistic insight into the role of mitochondria in tumorigenesis and identifying a novel therapeutic target in neoplasia. Copyright © 2013 Elsevier Ltd. All rights reserved.

Citation

Saverio Marchi, Laura Lupini, Simone Patergnani, Alessandro Rimessi, Sonia Missiroli, Massimo Bonora, Angela Bononi, Fabio Corrà, Carlotta Giorgi, Elena De Marchi, Federica Poletti, Roberta Gafà, Giovanni Lanza, Massimo Negrini, Rosario Rizzuto, Paolo Pinton. Downregulation of the mitochondrial calcium uniporter by cancer-related miR-25. Current biology : CB. 2013 Jan 07;23(1):58-63