CASIA OpenIR
p53-dependent upregulation of miR-16-2 by sanguinarine induces cell cycle arrest and apoptosis in hepatocellular carcinoma
Zhang, Beilei1,2; Wang, Xinan1; Deng, Jiacong3; Zheng, Haifeng1; Liu, Wei4; Chen, Si1; Tian, Jie1,5,6; Wang, Fu1
Source PublicationCANCER LETTERS
ISSN0304-3835
2019
Volume459Pages:50-58
Corresponding AuthorTian, Jie(jie.tian@ia.ac.cn) ; Wang, Fu(fwang@xidian.edu.cn)
AbstractMicroRNAs (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.
KeywordmiRNA-16 p53 Sanguinarine Cell cycle Apoptosis
DOI10.1016/j.canlet.2019.05.042
WOS KeywordTUMOR-SUPPRESSOR ; CANCER ; MICRORNAS ; PROGRESSION ; PATHWAYS ; MIR-21 ; GROWTH ; P53
Indexed BySCI
Language英语
Funding ProjectNational Natural Science Foundation of China[81772010] ; National Natural Science Foundation of China[81571721] ; National Key Research and Development Program of China (973 Program)[2017YFA0205202]
Funding OrganizationNational Natural Science Foundation of China ; National Key Research and Development Program of China (973 Program)
WOS Research AreaOncology
WOS SubjectOncology
WOS IDWOS:000480670800006
PublisherELSEVIER IRELAND LTD
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ia.ac.cn/handle/173211/27569
Collection中国科学院自动化研究所
Corresponding AuthorTian, Jie; Wang, Fu
Affiliation1.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
Corresponding Author AffilicationChinese Acad Sci, Inst Automat, CAS Key Lab Mol Imaging, Beijing 100190, Peoples R China
Recommended Citation
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.
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Zhang, Beilei]'s Articles
[Wang, Xinan]'s Articles
[Deng, Jiacong]'s Articles
Baidu academic
Similar articles in Baidu academic
[Zhang, Beilei]'s Articles
[Wang, Xinan]'s Articles
[Deng, Jiacong]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Zhang, Beilei]'s Articles
[Wang, Xinan]'s Articles
[Deng, Jiacong]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.