miR-193a-3p regulates the multi-drug resistance of bladder cancer by targeting the LOXL4 gene and the oxidative stress pathway.
miR-193a-3p regulates the multi-drug resistance of bladder cancer by targeting the LOXL4 gene and the oxidative stress pathway.
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miR-193a-3p通过靶向LOXL4基因和氧化应激途径调节膀胱癌的多药耐药性。
DOI：
10.1186/1476-4598-13-234
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发表时间：
2014-10-14
期刊：
影响因子：
37.3
通讯作者：
Zhu J
中科院分区：
文献类型：
--
作者：
Deng H;Lv L;Li Y;Zhang C;Meng F;Pu Y;Xiao J;Qian L;Zhao W;Liu Q;Zhang D;Wang Y;Zhang H;He Y;Zhu J
背景化疗耐药性是肿瘤化疗治疗的主要障碍，也是肿瘤研究和治疗中最大的挑战之一。结果通过对多药敏感（5637）和耐药（H-bc）膀胱癌细胞系的详细研究，我们发现miR-193 a-3 p [GenBank：NR_029710.1]促进了膀胱癌细胞的多药耐药性。我们进一步证明了赖氨酰氧化酶样4（LOXL 4）基因[GenBank：NM_032211.6]是miR-193 a-3 p的直接靶点，并执行前者对膀胱癌化疗耐药性的影响。细胞中miR-193 a-3 p或LOXL 4水平的强制逆转会显著影响氧化应激途径的活性，并且可能在LOXL 4基因的下游起作用，以传递miR-193 a-3 p对培养细胞和裸鼠肿瘤异种移植物中的多药耐药性的影响。我们的结果提供了一组新鉴定的miR-193 a-3 p/LOXL 4/氧化应激轴中的必需基因，作为指导性抗膀胱癌化疗的诊断靶点。
BackgroundChemoresistance is a major obstacle to the curative cancer chemotherapy and presents one of the most formidable challenges in both research and management of cancer.ResultsFrom the detailed studies of a multi-chemosensitive (5637) versus a chemoresistant (H-bc) bladder cancer cell lines, we showed that miR-193a-3p [GenBank: NR_029710.1] promotes the multi-chemoresistance of bladder cancer cells. We further demonstrated that lysyl oxidase-like 4 (LOXL4) gene [GenBank: NM_032211.6] is a direct target of miR-193a-3p and executes the former’s impact on bladder cancer chemoresistance. The Oxidative Stress pathway activity is drastically affected by a forced reversal of miR-193a-3p or LOXL4 levels in cell and may act at the downstream of LOXL4 gene to relay the miR-193a-3p’s impact on the multi-chemoresistance in both cultured cells and the tumor xenografts in nude mice.ConclusionsIn addition to a new mechanistic insight, our results provide a set of the essential genes in this newly identified miR-193a-3p/LOXL4/Oxidative Stress axis as the diagnostic targets for a guided anti-bladder cancer chemotherapy.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
14.9
作者：
Malhotra D;Portales-Casamar E;Singh A;Srivastava S;Arenillas D;Happel C;Shyr C;Wakabayashi N;Kensler TW;Wasserman WW;Biswal S
通讯作者：
Biswal S
影响因子：
1.4
作者：
Chang JS;Lara PN Jr;Pan CX
通讯作者：
Pan CX
影响因子：
4.8
作者：
Ma, Kelong;He, Yinghua;Zhu, Jingde
通讯作者：
Zhu, Jingde
影响因子：
11.2
作者：
Kozaki, Ken-ichi;Imoto, Issei;Inazawa, Johji
通讯作者：
Inazawa, Johji