Waltonitone inhibits proliferation of hepatoma cells and tumorigenesis via FXR-miR-22-CCNA2 signaling pathway

doi:10.18632/oncotarget.12614

	Waltonitone inhibits proliferation of hepatoma cells and tumorigenesis via FXR-miR-22-CCNA2 signaling pathway
	Yang, Fan 2; Gong, Junting 2; Wang, Guangyun 2; Chen, Peng 1; Yang, Li 2; Wang, Zhengtao 2
刊名	Oncotarget
	2016-11-15
卷号	7 期号:46 页码:75165-75175
ISSN号	1949-2553
DOI	10.18632/oncotarget.12614
文献子类	Article
英文摘要	Waltonitone (WA), an ursane-type pentacyclic triterpene extracted from Gentiana waltonii Burkill, was recently appeared to exert anti-tumor effect. However, the biological underpinnings underlying the role of WA in hepatocellular carcinoma (HCC) cells have not been completely elucidated. Our previous report indicated that the FXR-regulated miR-22-CCNA2 pathway contributed to the progression and development of HCC. Besides, a wide spectrum of microRNAs (miRNAs) could be up- or down-regulated upon WA treatment, including miR-22. Hence, we aimed to determine whether WA inhibited HCC cell proliferation via the FXR-miR-22-CCNA2 axis. In this study, we observed a significant downregulation of FXR and miR-22, along with upregulation of CCNA2 in 80 paired tumors relative to adjacent normal tissues of HCC subjects, which were obtained from the available GEO database in NCBI (GSE22058). Furthermore, we validated the expression patterns of these three targets in another set of HCC samples and found the highly correlation within each other. Additionally, our data demonstrated that WA induced miR-22 and repressed CCNA2 in HCC cells, which contributed to the cell proliferation arrest. In addition, evidence suggested that either miR-22 silencing or FXR knockdown reversed the diminished CCNA2 expression as well as cell proliferation inhibition caused by WA treatment and WA inhibited tumor masses in vivo in a subcutaneous xenograft mouse model of HCC. Overall, our data indicated that WA inhibited HCC cell proliferation and tumorigenesis through miR-22-regulated CCNA2 repression, which was at least partially through FXR modulation.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/266520]
专题	中国科学院上海药物研究所
作者单位	1.First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510006, China 2.The MOE Key Laboratory for Standardization of Chinese Medicines and the SHTCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China;
推荐引用方式 GB/T 7714	Yang, Fan,Gong, Junting,Wang, Guangyun,et al. Waltonitone inhibits proliferation of hepatoma cells and tumorigenesis via FXR-miR-22-CCNA2 signaling pathway[J]. Oncotarget,2016,7(46):75165-75175.
APA	Yang, Fan,Gong, Junting,Wang, Guangyun,Chen, Peng,Yang, Li,&Wang, Zhengtao.(2016).Waltonitone inhibits proliferation of hepatoma cells and tumorigenesis via FXR-miR-22-CCNA2 signaling pathway.Oncotarget,7(46),75165-75175.
MLA	Yang, Fan,et al."Waltonitone inhibits proliferation of hepatoma cells and tumorigenesis via FXR-miR-22-CCNA2 signaling pathway".Oncotarget 7.46(2016):75165-75175.