The miR-193a-3p regulated PSEN1 gene suppresses the multi-chemoresistance of bladder cancer
The miR-193a-3p regulated PSEN1 gene suppresses the multi-chemoresistance of bladder cancer
复制标题
miR-193a-3p调节的PSEN1基因抑制膀胱癌的多重化疗耐药。
DOI：
10.1016/j.bbadis.2014.12.014
复制
发表时间：
2015-03-01
影响因子：
6.2
通讯作者：
Zhu, Jingde
中科院分区：
文献类型：
--
作者：
Deng, Hui;Lv, Lei;Zhu, Jingde
化疗耐药性阻碍了根治性癌症治疗，我们对此的了解仍然不够充分。在化疗敏感(5637)和化疗耐药(H-BC)的膀胱癌细胞系差异表达的基因中，PSEN1基因(早老素1)的表达水平与耐药呈负相关，PSEN1基因是伽玛分泌酶的关键成分。小干扰RNA介导的PSEN1基因抑制细胞凋亡并使5637细胞减敏，而早老素1的过表达则使H-BC细胞对药物引发的细胞死亡敏感。PSEN1作为microRNA-193a-3p促进膀胱癌细胞多药耐药的直接靶点，可能通过激活DNA损伤反应通路，成为microRNA-193a-3p对膀胱癌多药耐药积极作用的重要执行者。除了机制上的见解，这个microRNA-193a-3p/PSEN1轴上的关键角色可能是膀胱癌有效化疗的诊断和/或治疗靶点。(C)2014爱思唯尔B.V.保留所有权利。
Chemoresistance prevents the curative cancer therapy, our understanding of which remains inadequate. Among the differentially expressed genes between the chemosensitive (5637) and chemoresistant (H-bc) bladder cancer cell lines, the expression level of the PSEN1 gene (presenilin 1), a key component of the gamma-secretase, is negatively correlated with chemoresistance. A small interfering RNA mediated repression of the PSEN1 gene suppresses cell apoptosis and de-sensitizes 5637 cells, while overexpression of the presenilin 1 sensitizes H-bc cells to the drug-triggered cell death. As a direct target of microRNA-193a-3p that promotes the multi-chemoresistance of the bladder cancer cell, PSEN1 acts as an important executor for the microRNA-193a-3p's positive impact on the multi-chemoresistance of bladder cancer, probably via its activating effect on DNA damage response pathway. In addition to the mechanistic insights, the key players in this microRNA-193a-3p/PSEN1 axis are likely the diagnostic and/or therapeutic targets for an effective chemotherapy of bladder cancer. (C) 2014 Elsevier B.V. All rights reserved.