The recently discovered mitochondrial calcium uniporter (MCU) promotes Ca2+ accumulation into the mitochondrial matrix [1, 2]. 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 Ca2+ uptake, while leaving other mitochondrial parameters and cytosolic Ca2+ signals unaffected. In human colon cancers and cancer-derived cells, miR-25 is overexpressed and MCU accordingly silenced. miR-25-dependent reduction of mitochondrial Ca2+ 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 Ca2+ signaling favors cancer cell survival, thus providing mechanistic insight into the role of mitochondria in tumorigenesis and identifying a novel therapeutic target in neoplasia. © 2013 Elsevier Ltd.

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

MARCHI, Saverio;LUPINI, Laura;PATERGNANI, Simone;RIMESSI, Alessandro;MISSIROLI, Sonia;BONORA, Massimo;BONONI, Angela;CORRA', Fabio;GIORGI, Carlotta;DE MARCHI, Elena;POLETTI, Federica;GAFA', Roberta;LANZA, Giovanni;NEGRINI, Massimo;PINTON, Paolo
2013

Abstract

The recently discovered mitochondrial calcium uniporter (MCU) promotes Ca2+ accumulation into the mitochondrial matrix [1, 2]. 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 Ca2+ uptake, while leaving other mitochondrial parameters and cytosolic Ca2+ signals unaffected. In human colon cancers and cancer-derived cells, miR-25 is overexpressed and MCU accordingly silenced. miR-25-dependent reduction of mitochondrial Ca2+ 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 Ca2+ signaling favors cancer cell survival, thus providing mechanistic insight into the role of mitochondria in tumorigenesis and identifying a novel therapeutic target in neoplasia. © 2013 Elsevier Ltd.
2013
Marchi, Saverio; Lupini, Laura; Patergnani, Simone; Rimessi, Alessandro; Missiroli, Sonia; Bonora, Massimo; Bononi, Angela; Corra', Fabio; Giorgi, Carlotta; DE MARCHI, Elena; Poletti, Federica; Gafa', Roberta; Lanza, Giovanni; Negrini, Massimo; Rizzuto, R; Pinton, Paolo
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1747497
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