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p53-dependent upregulation of miR-16-2 by sanguinarine induces cell cycle arrest and apoptosis in hepatocellular carcinoma

文献类型：期刊论文

作者Zhang, Beilei1,2; Wang, Xinan1; Deng, Jiacong3; Zheng, Haifeng1; Liu, Wei4; Chen, Si1; Tian, Jie1,5,6; Wang, Fu1
刊名CANCER LETTERS
出版日期2019
卷号459页码:50-58
关键词miRNA-16 p53 Sanguinarine Cell cycle Apoptosis
ISSN号0304-3835
DOI10.1016/j.canlet.2019.05.042
通讯作者Tian, Jie(jie.tian@ia.ac.cn) ; Wang, Fu(fwang@xidian.edu.cn)
英文摘要MicroRNAs (miRNAs) were involved in cancer progression, and the targeting of miRNAs by natural agents has opened avenues for cancer treatment and drug development. miR-16 functions as a tumor suppressor and is frequently deleted or downregulated in various human cancers, including hepatocellular carcinoma (HCC). In the present study, we employed a miR-16-responsive luciferase reporter to screen candidate compounds that modulate miR-16 expression from a natural product library. One compound, sanguinarine (SG), was capable of activating miR-16 in HCC cells with wildtype or mutated p53 expression but not in p53-deleted HCC cells. Mechanistic investigations revealed that SG increased p53 occupancy on the miR-16-2 promoter and decreased the expression of miR-16 target genes, including Bcl-2 and cyclin D1. Moreover, SG significantly inhibited HCC cell proliferation in a p53-dependent manner by inducing cell cycle arrest and reactive oxygen species (ROS)-associated apoptosis. Silencing miR-16 by treatment with anti-miR16 miRNA inhibitors rescued the cell viability repression effect caused by SG. Importantly, SG dramatically suppressed tumor growth in an HCC xenograft model, with little cytotoxicity. Taken together, our results provide a preclinical proof-of-concept for SG as a potential strategy for HCC treatment based on the restoration of miR-16 tumor suppressor function.
WOS关键词TUMOR-SUPPRESSOR ; CANCER ; MICRORNAS ; PROGRESSION ; PATHWAYS ; MIR-21 ; GROWTH ; P53
资助项目National Natural Science Foundation of China[81772010] ; National Natural Science Foundation of China[81571721] ; National Key Research and Development Program of China (973 Program)[2017YFA0205202]
WOS研究方向Oncology
语种英语
WOS记录号WOS:000480670800006
出版者ELSEVIER IRELAND LTD
资助机构National Natural Science Foundation of China ; National Key Research and Development Program of China (973 Program)
源URL[http://ir.ia.ac.cn/handle/173211/27568]  
专题自动化研究所_中国科学院分子影像重点实验室
通讯作者Tian, Jie; Wang, Fu
作者单位1.Xidian Univ, Engn Res Ctr Mol & Neuro Imaging, Sch Life Sci & Technol, Minist Educ, Xian 710071, Shaanxi, Peoples R China
2.Fourth Mil Med Univ, Tangdu Hosp, Dept Gynecol & Obstet, Xian 710038, Shaanxi, Peoples R China
3.Fujian Normal Univ, Sch Ocean Sci & Biochem Engn, Fuqing Branch, Fuqing 350300, Fujian, Peoples R China
4.Fourth Mil Med Univ, Xijing Hosp, Dept Hepatobiliary Surg, Xian 710032, Shaanxi, Peoples R China
5.Chinese Acad Sci, Inst Automat, CAS Key Lab Mol Imaging, Beijing 100190, Peoples R China
6.Beihang Univ, Sch Med, Beijing Adv Innovat Ctr Big Data Based Precis Med, Beijing 100190, Peoples R China
推荐引用方式
GB/T 7714		 Zhang, Beilei,Wang, Xinan,Deng, Jiacong,et al. p53-dependent upregulation of miR-16-2 by sanguinarine induces cell cycle arrest and apoptosis in hepatocellular carcinoma[J]. CANCER LETTERS,2019,459:50-58.
APA Zhang, Beilei.,Wang, Xinan.,Deng, Jiacong.,Zheng, Haifeng.,Liu, Wei.,...&Wang, Fu.(2019).p53-dependent upregulation of miR-16-2 by sanguinarine induces cell cycle arrest and apoptosis in hepatocellular carcinoma.CANCER LETTERS,459,50-58.
MLA Zhang, Beilei,et al."p53-dependent upregulation of miR-16-2 by sanguinarine induces cell cycle arrest and apoptosis in hepatocellular carcinoma".CANCER LETTERS 459(2019):50-58.

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来源：自动化研究所

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