The miR-491-3p/Sp3/ABCB1 axis attenuates multidrug resistance of hepatocellular carcinoma

doi:10.1016/j.canlet.2017.08.027

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	The miR-491-3p/Sp3/ABCB1 axis attenuates multidrug resistance of hepatocellular carcinoma
	Zhao, Yang 1,2; Qi, Xinming1,2 ; Chen, Jing1,2 ; Wei, Wenxin 3; Yu, Cunzhi 1,2; Yan, Hong 1,2; Pu, Mengfan 1,2; Li, Yu 1,2; Miao, Lingling 1,2; Li, Chunzhu 1,2
刊名	CANCER LETTERS
	2017-11-01
卷号	408 页码:102-111
关键词	Hepatocellular carcinoma ABCB1 Sp3 miR-491-3p Multidrug resistance
ISSN号	0304-3835
DOI	10.1016/j.canlet.2017.08.027
文献子类	Article
英文摘要	As one of main obstacles in the treatment and prognosis of hepatocellular carcinoma (HCC), multidrug resistance (MDR) is usually associated with the overexpression of the drug efflux pump P-glycoprotein (P-gp/ABCB1) which is responsible for reducing the intracellular concentration of chemotherapeutic agents. In current work, we discovered the novel role of miR-491-3p in ABCB1-mediated multidrug resistance in HCC and revealed the underlying mechanism in which miR-491-3p downregulated the expression of ABCB1 and its transcription factor Sp3 by directly targeting their 3'-UTR. Moreover, overexpressing ABCB1 or Sp3 reversed the sensitivity to chemotherapeutics in Hep3B cells induced by miR-491-3p, confirming miR-491-3p/Sp3/ABCB1 regulatory loop plays an important role in enhancing the drugs sensitivity of HCC. Meanwhile, the discovery of that the expression level of miR-491-3p was inversely correlated with that of ABCB1 and Sp3 in HCC cell lines and clinical samples pointed out the possibility of miR-491-3p in clinical use. In summary, our results reveal a pivotal role of miR-491-3p in the regulation of MDR in HCC, and suggest the potential application of miR-491-3p as a therapeutic strategy for modulating MDR in cancer cells. (C) 2017 Elsevier B.V. All rights reserved.
资助项目	National Science and Technology Major Project of China[2015ZX09102005]
WOS关键词	BREAST-CANCER CELLS ; DRUG-SENSITIVITY ; ABC TRANSPORTERS ; GENE-EXPRESSION ; GASTRIC-CANCER ; P-GLYCOPROTEIN ; PACLITAXEL ; MICRORNAS ; MDR1 ; CHEMOSENSITIVITY
WOS研究方向	Oncology
语种	英语
出版者	ELSEVIER IRELAND LTD
WOS记录号	WOS:000413616400013
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272427]
专题	药物安全性评价中心中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Li, Chunzhu; Ren, Jin
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Univ Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res, State Key Lab Drug Res, Beijing 100049, Peoples R China; 3.Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Dept Hepat Surg, Shanghai 200438, Peoples R China
推荐引用方式 GB/T 7714	Zhao, Yang,Qi, Xinming,Chen, Jing,et al. The miR-491-3p/Sp3/ABCB1 axis attenuates multidrug resistance of hepatocellular carcinoma[J]. CANCER LETTERS,2017,408:102-111.
APA	Zhao, Yang.,Qi, Xinming.,Chen, Jing.,Wei, Wenxin.,Yu, Cunzhi.,...&Ren, Jin.(2017).The miR-491-3p/Sp3/ABCB1 axis attenuates multidrug resistance of hepatocellular carcinoma.CANCER LETTERS,408,102-111.
MLA	Zhao, Yang,et al."The miR-491-3p/Sp3/ABCB1 axis attenuates multidrug resistance of hepatocellular carcinoma".CANCER LETTERS 408(2017):102-111.