title: Downregulation of the mitochondrial calcium uniporter by cancer-related miR-25.
abstract: 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.
authors.affiliation: Section of General Pathology, Department of Morphology, Surgery and Experimental Medicine, Interdisciplinary Center for the Study of Inflammation, Laboratory for Technologies of Advanced Therapies, University of Ferrara, 44121 Ferrara, Italy.
authors.forename: Saverio
authors.initials: S
authors.lastname: Marchi
authors.forename: Laura
authors.initials: L
authors.lastname: Lupini
authors.forename: Simone
authors.initials: S
authors.lastname: Patergnani
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rimessi
authors.forename: Sonia
authors.initials: S
authors.lastname: Missiroli
authors.forename: Massimo
authors.initials: M
authors.lastname: Bonora
authors.forename: Angela
authors.initials: A
authors.lastname: Bononi
authors.forename: Fabio
authors.initials: F
authors.lastname: Corrà
authors.forename: Carlotta
authors.initials: C
authors.lastname: Giorgi
authors.forename: Elena
authors.initials: E
authors.lastname: De Marchi
authors.forename: Federica
authors.initials: F
authors.lastname: Poletti
authors.forename: Roberta
authors.initials: R
authors.lastname: Gafà
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lanza
authors.forename: Massimo
authors.initials: M
authors.lastname: Negrini
authors.forename: Rosario
authors.initials: R
authors.lastname: Rizzuto
authors.forename: Paolo
authors.initials: P
authors.lastname: Pinton
mesh_terms: D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling / Q000235:genetics; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*
chemical_list: D015220:Calcium Channels; C543351:MIRN25 microRNA, human; D035683:MicroRNAs; C034703:mitochondrial calcium uniporter