Downregulation of the Mitochondrial Calcium Uniporter by Cancer-Related miR-25.

Section of General Pathology, Department of Morphology, Surgery and Experimental Medicine, Interdisciplinary Center for the Study of Inflammation (ICSI), Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, 44121 Ferrara, Italy.
Current biology: CB (Impact Factor: 10.99). 12/2012; DOI: 10.1016/j.cub.2012.11.026
Source: PubMed

ABSTRACT The recently discovered mitochondrial calcium uniporter (MCU) promotes Ca(2+) 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 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.

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May 21, 2014