PIWIL1 promotes gastric cancer via a piRNA-independent mechanism

doi:10.1073/pnas.2008724117

	PIWIL1 promotes gastric cancer via a piRNA-independent mechanism
	Shi, Shuo1 ; Yang, Zhen-Zhen1 ; Liu, Sanhong1 ; Yang, Fan1 ; Lin, Haifan 2,3
	2020-09-08
发表期刊	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (IF:9.4[JCR-2023],10.8[5-Year])
ISSN	0027-8424
卷号	117 期号:36 页码:22390-22401
DOI	10.1073/pnas.2008724117
摘要	Targeted cancer therapy aims to achieve specific elimination of cancerous but not normal cells. Recently, PIWI proteins, a subfamily of the PAZ-PIWI domain (PPD) protein family, have emerged as promising candidates for targeted cancer therapy. PPD proteins are essential for small noncoding RNA pathways. The Argonaute subfamily partners with microRNA and small interfering RNA, whereas the PIWI subfamily partners with PIWI-interacting RNA (piRNA). Both PIWI proteins and piRNA are mostly expressed in the germline and best known for their function in transposon silencing, with no detectable function in mammalian somatic tissues. However, PIWI proteins become aberrantly expressed in multiple types of somatic cancers, thus gaining interest in targeted therapy. Despite this, little is known about the regulatory mechanism of PIWI proteins in cancer. Here we report that one of the four PIWI proteins in humans, PIWIL1, is highly expressed in gastric cancer tissues and cell lines. Knocking out the PIWIL1 gene (PIWIL1-KO) drastically reduces gastric cancer cell proliferation, migration, metastasis, and tumorigenesis. RNA deep sequencing of gastric cancer cell line SNU-1 reveals that KO significantly changes the transcriptome, causing the up-regulation of most of its associated transcripts. Surprisingly, few bona fide piRNAs exist in gastric cancer cells. Furthermore, abolishing the piRNA-binding activity of PIWIL1 does not affect its oncogenic function. Thus, PIWIL1 function in gastric cancer cells is independent of piRNA. This piRNA-independent regulation involves interaction with the UPF1-mediated nonsense-mediated mRNA decay (NMD) mechanism. Altogether, our findings reveal a piRNA-independent function of PIWIL1 in promoting gastric cancer.
关键词	gastric cancer PIWI piRNA human nonsense-mediated mRNA decay
收录类别	SCI ; SCIE
语种	英语
资助项目	Yangfan Grant[2018X0301-103-01]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000572968600010
出版者	NATL ACAD SCIENCES
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/123574
专题	免疫化学研究所_特聘教授组_干细胞生物学实验室免疫化学研究所_特聘教授组_Erez Lieberman Aiden组
通讯作者	Lin, Haifan
作者单位	1.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China; 2.Yale Univ, Sch Med, Yale Stem Cell Ctr, 333 Cedar St, New Haven, CT 06519 USA; 3.Yale Univ, Sch Med, Dept Cell Biol, 333 Cedar St, New Haven, CT 06519 USA
第一作者单位	免疫化学研究所
第一作者的第一单位	免疫化学研究所
推荐引用方式 GB/T 7714	Shi, Shuo,Yang, Zhen-Zhen,Liu, Sanhong,et al. PIWIL1 promotes gastric cancer via a piRNA-independent mechanism[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2020,117(36):22390-22401.
APA	Shi, Shuo,Yang, Zhen-Zhen,Liu, Sanhong,Yang, Fan,&Lin, Haifan.(2020).PIWIL1 promotes gastric cancer via a piRNA-independent mechanism.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,117(36),22390-22401.
MLA	Shi, Shuo,et al."PIWIL1 promotes gastric cancer via a piRNA-independent mechanism".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 117.36(2020):22390-22401.