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膀胱癌中的线粒体功能障碍:探究其作为疾病标志物和潜在治疗靶点的作用。

Mitochondrial dysfunctions in bladder cancer: Exploring their role as disease markers and potential therapeutic targets.

作者信息

Cormio Antonella, Sanguedolce Francesca, Musicco Clara, Pesce Vito, Calò Giuseppe, Bufo Pantaleo, Carrieri Giuseppe, Cormio Luigi

机构信息

Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy.

Department of Pathology, University of Foggia, Foggia, Italy.

出版信息

Crit Rev Oncol Hematol. 2017 Sep;117:67-72. doi: 10.1016/j.critrevonc.2017.07.001. Epub 2017 Jul 11.

Abstract

Bladder cancer (BC) is a major cause of mortality worldwide as it currently lacks fully reliable markers of disease outcome and effective molecular targets for therapy. Mitochondria play a key role in cell metabolism but the role of mitochondrial dysfunctions in BC has been scarcely investigated. In this review, we explored current evidence for the potential role of mitochondrial DNA (mtDNA) alterations (point mutations and copy number) as disease markers in BC. Some germline mtDNA mutations detectable in blood could represent a non-invasive tool to predict the risk of developing BC. MtDNA copy number and tumor specific mtDNA mutations and RNAs showed encouraging results as novel molecular markers for early detection of BC in body fluids. Moreover, mitochondrial proteins Lon protease, Mitofusin-2, and TFAM may have prognostic/predictive value and may represent potential therapeutic targets. A deeper understanding of mitochondrial dysfunctions in BC could therefore provide novel opportunities for targeted therapeutic strategies.

摘要

膀胱癌(BC)是全球主要的致死原因之一,因为目前它缺乏完全可靠的疾病预后标志物和有效的治疗分子靶点。线粒体在细胞代谢中起关键作用,但线粒体功能障碍在膀胱癌中的作用鲜有研究。在本综述中,我们探讨了线粒体DNA(mtDNA)改变(点突变和拷贝数)作为膀胱癌疾病标志物潜在作用的现有证据。在血液中可检测到的一些种系mtDNA突变可能代表一种预测患膀胱癌风险的非侵入性工具。mtDNA拷贝数、肿瘤特异性mtDNA突变和RNA作为体液中早期检测膀胱癌的新型分子标志物显示出令人鼓舞的结果。此外,线粒体蛋白Lon蛋白酶、线粒体融合蛋白2和线粒体转录因子A可能具有预后/预测价值,并且可能代表潜在的治疗靶点。因此,更深入地了解膀胱癌中的线粒体功能障碍可为靶向治疗策略提供新的机会。

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