Sepiapterin reductase promotes hepatocellular carcinoma progression via FoxO3a/Bim signaling in a nonenzymatic manner

doi:10.1038/s41419-020-2471-7

	Sepiapterin reductase promotes hepatocellular carcinoma progression via FoxO3a/Bim signaling in a nonenzymatic manner
	Wu, Yao 1; Du, Hongzhi 2; Zhan, Meixiao 3; Wang, Hongxv 1; Chen, Peng 4; Du, Danyu 1; Liu, Xinyi 5; Huang, Xingxv 5; Ma, Pengcheng 6; Peng, Dezheng 6
刊名	CELL DEATH & DISEASE
	2020-04-20
卷号	11 期号:4 页码:14
ISSN号	2041-4889
DOI	10.1038/s41419-020-2471-7
通讯作者	Ding, Jian(jding@simm.ac.cn) ; Lu, Ligong(luligong1969@126.com) ; Jiang, Jingwei(jiangjingwei@cpu.edu.cn)
英文摘要	Sepiapterin reductase plays an enzymatic role in the biosynthesis of tetrahydrobiopterin, which is reported in limited studies to regulate the progression of several tumors. However, the role of sepiapterin reductase in hepatocellular carcinoma remains largely unknown. Here, we found that sepiapterin reductase was frequently highly expressed in human hepatocellular carcinoma, which was significantly associated with higher T stage, higher tumor node metastasis stage, and even shorter survival of hepatocellular carcinoma patients. Furthermore, cell and animal experiments showed that sepiapterin reductase depletion inhibited cancer cell proliferation and promoted cancer cell apoptosis. Importantly, the results suggested that sepiapterin reductase enzymatic activity was not necessary for the progression of hepatocellular carcinoma, based on the comparison between SMMC-7721 and SMMC-7721 containing sepiapterin reductase mutant. Moreover, we showed that sepiapterin reductase regulated the development of hepatocellular carcinoma via the FoxO3a/Bim-signaling pathway. Collectively, our study suggests that sepiapterin reductase controls hepatocellular carcinoma progression via FoxO3a/Bim signaling in a nonenzymatic manner, which provides a potential prognostic factor and therapeutic strategy for hepatocellular carcinoma.
资助项目	National Key Research and Development Program of China[2017YFA0205200] ; National Natural Science Foundation of China[81773766] ; National Natural Science Foundation of China[81903845] ; Science and Technology Research Project of Hubei Provincial Department of Education[Q20192007] ; Natural Science Foundation of Jiangsu Province[SBK2018021376] ; Double First-Class University project[CPU2018GY38] ; Graduate Student Research Innovation Projects in Jiangsu Province[KYCX17_0691]
WOS关键词	CANCER-CELL MIGRATION ; TETRAHYDROBIOPTERIN ; BIM ; GROWTH ; PROLIFERATION ; REVEALS ; TARGET ; LSD1
WOS研究方向	Cell Biology
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000529212000003
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/280584]
专题	中国科学院上海药物研究所
通讯作者	Ding, Jian; Lu, Ligong; Jiang, Jingwei
作者单位	1.China Pharmaceut Univ, Jiangsu Key Lab Drug Screening, Nanjing, Peoples R China 2.Hubei Univ Chinese Med, Sch Pharm, 16 Huangjiahu Rd West, Wuhan, Peoples R China 3.Jinan Univ, Zhuhai Hosp, Zhuhai Peoples Hosp, Zhuhai Intervent Med Ctr,Zhuhai Precis Med Ctr, Zhuhai, Peoples R China 4.Nanchang Univ, Dept Neurosurg, Affiliated Hosp 2, Nanchang, Jiangxi, Peoples R China 5.ShanghaiTech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai, Peoples R China 6.Peking Union Med Coll, Chinese Acad Med Sci, Inst Dermatol, 12 Jiangwangmiao St, Nanjing, Peoples R China 7.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Wu, Yao,Du, Hongzhi,Zhan, Meixiao,et al. Sepiapterin reductase promotes hepatocellular carcinoma progression via FoxO3a/Bim signaling in a nonenzymatic manner[J]. CELL DEATH & DISEASE,2020,11(4):14.
APA	Wu, Yao.,Du, Hongzhi.,Zhan, Meixiao.,Wang, Hongxv.,Chen, Peng.,...&Jiang, Jingwei.(2020).Sepiapterin reductase promotes hepatocellular carcinoma progression via FoxO3a/Bim signaling in a nonenzymatic manner.CELL DEATH & DISEASE,11(4),14.
MLA	Wu, Yao,et al."Sepiapterin reductase promotes hepatocellular carcinoma progression via FoxO3a/Bim signaling in a nonenzymatic manner".CELL DEATH & DISEASE 11.4(2020):14.