Downregulation of the mitochondrial calcium uniporter by cancer-related miR-25.
Downregulation of the mitochondrial calcium uniporter by cancer-related miR-25.
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DOI：
10.1016/j.cub.2012.11.026
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发表时间：
2013-01-07
期刊：
影响因子：
9.2
通讯作者：
Pinton, Paolo
中科院分区：
文献类型：
--
作者：
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, Rosario;Pinton, Paolo
最近发现的线粒体钙单向转运体（MCU）促进Ca 2+积累到线粒体基质中。我们在计算机上鉴定了miR-25作为癌症相关的MCU靶向microRNA家族，并证明其在HeLa细胞中的过表达大大降低了MCU水平和线粒体Ca 2+摄取，而其他线粒体参数和胞质Ca 2+信号不受影响。在人类结肠癌和癌源性细胞中，miR-25过表达，MCU因此沉默。miR-25依赖性的线粒体Ca 2+摄取减少与对凋亡挑战的抗性相关，并且可以通过抗miR-25过表达逆转。总的来说，数据表明，线粒体Ca 2+信号的microRNA靶向有利于癌细胞的存活，从而提供了线粒体在肿瘤发生中的作用的机制见解，并确定了一种新的肿瘤治疗靶点。miR-25调节细胞内钙稳态线粒体钙单向转运体（MCU）是miR-25的靶点MCU在细胞凋亡和肿瘤发生中起关键作用MCU在不同的癌细胞系和人结肠腺癌中下调
The recently discovered mitochondrial calcium uniporter (MCU) promotes Ca2+ 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 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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线粒体网络和内质网之间的结构和功能联系。
DOI：
10.1016/j.biocel.2009.04.010
发表时间：
2009-10
影响因子：
4
作者：
Giorgi, Carlotta;De Stefani, Diego;Bononi, Angela;Rizzuto, Rosario;Pinton, Paolo
通讯作者：
Pinton, Paolo
影响因子：
4.2
作者：
Zhang, Haiyan;Zuo, Zhi;Zhu, Zhiling
通讯作者：
Zhu, Zhiling
影响因子：
37.3
作者：
Lanza G;Ferracin M;Gafà R;Veronese A;Spizzo R;Pichiorri F;Liu CG;Calin GA;Croce CM;Negrini M
通讯作者：
Negrini M
影响因子：
3.7
作者：
Dong H;Paquette M;Williams A;Zoeller RT;Wade M;Yauk C
通讯作者：
Yauk C
内膜的四十千克蛋白是线粒体钙Uniporter。
影响因子：
64.8
作者：
De Stefani, Diego;Raffaello, Anna;Teardo, Enrico;Szabo, Ildiko;Rizzuto, Rosario
通讯作者：
Rizzuto, Rosario