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

被引：224

作者：

Marchi, Saverio ^{[1
]}

Lupini, Laura

Patergnani, Simone ^{[1
]}

Rimessi, Alessandro ^{[1
]}

Missiroli, Sonia ^{[1
]}

Bonora, Massimo ^{[1
]}

Bononi, Angela ^{[1
]}

Corra, Fabio

Giorgi, Carlotta ^{[1
]}

De Marchi, Elena ^{[1
]}

Poletti, Federica ^{[1
]}

Gafa, Roberta ^{[2
]}

Lanza, Giovanni ^{[2
]}

Negrini, Massimo

Rizzuto, Rosario ^{[3
,4
]}

Pinton, Paolo ^{[1
]}

机构：

[1] Univ Ferrara, Sect Gen Pathol, Dept Morphol Surg & Expt Med, ICSI,Lab Technol Adv Therapies LTTA, I-44121 Ferrara, Italy

[2] Univ Ferrara, Anat Pathol Sect, Dept Morphol Surg & Expt Med, I-44121 Ferrara, Italy

[3] Univ Padua, Dept Biomed Sci, I-35129 Padua, Italy

[4] CNR, Inst Neurosci, I-35129 Padua, Italy

来源：

CURRENT BIOLOGY | 2013年 / 23卷 / 01期

基金：

美国国家卫生研究院;

关键词：

ENDOPLASMIC-RETICULUM; CA2+; APOPTOSIS; MICRORNAS; MECHANISMS; PROTEIN;

D O I：

10.1016/j.cub.2012.11.026

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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 mitochondria! 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 mitochondria! 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.

引用

页码：58 / 63

页数：6

共 26 条

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