miR-193a-3p regulates the multi-drug resistance of bladder cancer by targeting the LOXL4 gene and the Oxidative Stress pathway

Molecular Cancer

Research

Youguang Pu¹  Lei Lv¹  Hui Deng¹  Jingde Zhu²  Yinghua He³  Hongyu Zhang³  Yang Li⁴  Weidong Zhao⁵  Daming Zhang⁶  Yingwei Wang⁷  Fang Meng⁸  Liting Qian⁸  Jun Xiao⁹  Cheng Zhang^1,10  Qi Liu^1,11 

[1] Cancer Epigenetics Program, Anhui Cancer Hospital, 230031, Hefei, Anhui, China;Cancer Epigenetics Program, Anhui Cancer Hospital, 230031, Hefei, Anhui, China;Cancer Epigenetics Program, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University, 200032, Shanghai, China;Cancer Epigenetics Program, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University, 200032, Shanghai, China;Department of Biology, School of Life Science, Anhui Medical University, 230031, Hefei, Anhui, China;Department of Gynecologic Cancer, Anhui Cancer Hospital, 230031, Hefei, Anhui, China;Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China;Department of Pathology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China;Department of Radiotherapy, Anhui Cancer Hospital, 230031, Hefei, Anhui, China;Department of Urology, Anhui provincial hospital, Hefei, China;Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China;School of Life Science and Technology, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, 150001, Harbin, Heilongjiang, China;

关键词: LOXL4;    miR-193a-3p;    Chemoresistance;    Bladder cancer;    Oxidative stress pathway;   

DOI  :  10.1186/1476-4598-13-234

 received in 2014-07-10, accepted in 2014-10-06,  发布年份 2014

来源: Springer

【 摘 要 】

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.

【 授权许可】

Unknown   
© Deng et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.