MiR-193a-3p promotes the multi-chemoresistance of bladder cancer by targeting the HOXC9 gene
MiR-193a-3p promotes the multi-chemoresistance of bladder cancer by targeting the HOXC9 gene
复制标题
MiR-193a-3p通过靶向HOXC9基因促进膀胱癌的多重化疗耐药。
DOI：
10.1016/j.canlet.2014.11.002
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发表时间：
2015-02-01
期刊：
影响因子：
9.7
通讯作者：
Zhu, Jingde
中科院分区：
文献类型：
--
作者：
Lv, Lei;Li, Yang;Zhu, Jingde
化疗耐药阻碍了治愈性癌症的化疗，对癌症研究人员和临床医生都提出了一个巨大的挑战。我们之前的研究表明，miR-193a-3p通过抑制其三个靶基因：SRSF2、PLAU和HIC2，促进膀胱癌细胞的多重化疗耐药。本研究通过对多化学敏感（5637）和耐药（H-bc）膀胱癌细胞系在细胞培养和肿瘤-异种移植/裸鼠系统中的系统研究，发现同源盒C9 （HOXC9）基因作为新的直接靶点，也执行miR-193a-3p对膀胱癌化疗耐药的促进作用。与药物引发的细胞死亡的变化相平行，膀胱癌细胞中miR-193a-3p或HOXC9水平的强制逆转导致DNA损伤反应和氧化应激途径的活性急剧改变。我们的研究结果除了提供了新的机制见解外，还提供了miR-193a-3p/HOXC9/DNA损伤反应/氧化应激通路轴上的一组必需基因作为指导抗膀胱癌化疗的诊断靶点。(c) 2014年Elsevier Ireland Ltd.出版。
Chemoresistance prevents the curative cancer chemotherapy and presents a formidable challenge for both cancer researchers and clinicians. We have previously shown that miR-193a-3p promotes the multi-chemoresistance of bladder cancer cells via repressing its three target genes: SRSF2, PLAU and HIC2. Here, we showed that as a new direct target, the homeobox C9 (HOXC9) gene also executes the promoting effect of miR-193a-3p on the bladder cancer chemoresistance from a systematic study of multi-chemosensitive (5637) and resistant (H-bc) bladder cancer cell lines in both cell culture and tumor-xenograft/nude mice system. Paralleled with the changes in the drug-triggered cell death, the activities of both DNA damage response and oxidative stress pathways were drastically altered by a forced reversal of miR-193a-3p or HOXC9 levels in bladder cancer cells. In addition to a new mechanistic insight, our results provide a set of the essential genes in the miR-193a-3p/HOXC9/DNA damage response/oxidative stress pathway axis as the diagnostic targets for the guided anti-bladder cancer chemotherapy. (c) 2014 Published by Elsevier Ireland Ltd.