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微小 RNA 介导的自噬信号网络与癌症化疗耐药性。

MicroRNA-mediated autophagic signaling networks and cancer chemoresistance.

机构信息

1 Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University , Nanjing, China .

出版信息

Cancer Biother Radiopharm. 2013 Oct;28(8):573-8. doi: 10.1089/cbr.2012.1460. Epub 2013 Jul 10.

Abstract

Chemoresistance remains a major clinical obstacle to successful cancer treatment and brings about poor prognosis of the patients, yet the underlying mechanisms have not been entirely understood. MicroRNAs (miRNAs) are a new class of small noncoding RNAs that may play an essential role for regulation of programmed cell death, which consists of apoptosis and autophagy. Autophagy refers to an evolutionarily conserved catabolic process in which, a cell degrades long-lived proteins and damaged organelles. Recently, increasing evidence indicates that autophagy is associated with multiple cancer-related pathways, including resistance to chemotherapeutics. Moreover, manipulation of miRNA expression levels may increase cell sensitivity to cytotoxic drugs through targeting the autophagic signaling pathway. In this review, we summarized the recent findings concerning miRNAs involved in autophagy, mainly focused on the mechanism of miRNA modulation at different autophagic stages, the crucial role of miRNAs in the interconnection between autophagy and apoptosis, and the potential of miRNAs to overcome chemoresistance by targeting autophagic pathways.

摘要

耐药性仍然是癌症治疗成功的主要临床障碍,给患者带来不良预后,但其中的潜在机制尚未完全阐明。微小 RNA(miRNA)是一类新的小非编码 RNA,可能在程序性细胞死亡的调控中发挥重要作用,程序性细胞死亡包括细胞凋亡和自噬。自噬是一种进化上保守的分解代谢过程,其中细胞降解寿命长的蛋白质和受损的细胞器。最近,越来越多的证据表明,自噬与多种与癌症相关的途径有关,包括对化疗药物的耐药性。此外,通过靶向自噬信号通路,miRNA 表达水平的调控可能会增加细胞对细胞毒性药物的敏感性。在这篇综述中,我们总结了与自噬相关的 miRNA 的最新发现,主要集中在 miRNA 对不同自噬阶段的调控机制、miRNA 在自噬和细胞凋亡之间相互联系中的关键作用以及 miRNA 通过靶向自噬途径克服化疗耐药性的潜力。

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