Institutional Repository of Chinese Acad Sci, Inst Automat, CAS Key Lab Mol Imaging, Beijing 100190, Peoples R China
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 | |
发表期刊 | CANCER LETTERS |
ISSN | 0304-3835 |
2019 | |
卷号 | 459页码:50-58 |
通讯作者 | Tian, Jie(jie.tian@ia.ac.cn) ; Wang, Fu(fwang@xidian.edu.cn) |
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. |
关键词 | miRNA-16 p53 Sanguinarine Cell cycle Apoptosis |
DOI | 10.1016/j.canlet.2019.05.042 |
关键词[WOS] | TUMOR-SUPPRESSOR ; CANCER ; MICRORNAS ; PROGRESSION ; PATHWAYS ; MIR-21 ; GROWTH ; P53 |
收录类别 | SCI |
语种 | 英语 |
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] ; 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] |
项目资助者 | National Natural Science Foundation of China ; National Key Research and Development Program of China (973 Program) |
WOS研究方向 | Oncology |
WOS类目 | Oncology |
WOS记录号 | WOS:000480670800006 |
出版者 | ELSEVIER IRELAND LTD |
七大方向——子方向分类 | 医学影像处理与分析 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://ir.ia.ac.cn/handle/173211/27569 |
专题 | 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 |
通讯作者单位 | 中国科学院分子影像重点实验室 |
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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