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Marchi, Saverio; Lupini, Laura; Patergnani, Simone; Rimessi, Alessandro; Missiroli, Sonia; Bonora, Massimo; Bononi, Angela; Corrà, Fabio; Giorgi, Carlotta; De Marchi, Elena; Poletti, Federica; Gafà, Roberta; Lanza, Giovanni; Negrini, Massimo; Rizzuto, Rosario; Pinton, Paolo
CB/Current biology, 01/2013, Letnik: 23, Številka: 1Journal Article
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. ► miR-25 regulates intracellular calcium homeostasis ► Mitochondrial calcium uniporter (MCU) is a target of miR-25 ► MCU plays a critical role in apoptosis and tumorigenesis ► MCU is downregulated in different cancer cell lines and in human colonic adenocarcinoma
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in: SICRIS
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