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Vimentin binds to a novel tumor suppressor protein, GSPT1-238aa, encoded by circGSPT1 with a selective encoding priority to halt autophagy in gastric carcinoma

文献类型：期刊论文

作者Hu, Fan4; Peng, Yin4; Chang, Shanshan4; Luo, Xiaonuan4; Yuan, Yuan4; Zhu, Xiaohui4; Xu, Yidan4; Du, Kaining4; Chen, Yang4; Deng, Shiqi4
刊名CANCER LETTERS
出版日期2022-10-01
卷号545页码:14
ISSN号0304-3835
关键词Circular RNAs circGSPT1 Autophagy Translation Gastric cancer
DOI10.1016/j.canlet.2022.215826
英文摘要Circular RNAs (circRNAs) are covalently closed, endogenous molecules that are widespread in eukaryotes. Recent evidence indicates that circRNAs play important roles in carcinogenesis. Several circRNAs have been reported to comprise translatable RNA; however, whether circRNAs encode functional proteins remains unknown. In our study, circRNA sequencing was carried out using five pathologically diagnosed gastric carcinoma (GC) samples and their paired adjacent normal tissues, we characterized the circRNA GSPT1 (circGSPT1), which is expressed at low levels in GC. Antibody detections, and mass spectrometry were used to validate active circRNA translation. The spanning junction open reading frame in circGSPT1, driven by an internal ribosome entry site (IRES), encodes a functional peptide, termed GSPT1-238aa. Interestingly, GSPT1-238aa tends to select the start codon used to initiate translation. This is the first finding of selective translation driven by IRES. CircGSPT1 and GSPT1-238aa halted the proliferation, migration, and invasion in GC cells in vitro. We also confirmed that the vimentin/Beclin1/14-3-3 complex interacts with GSPT1-238aa and modulates autophagy via the PI3K/AKT/mTOR signaling pathway in GC cells. Our study reveals that GSPT1-238aa, a novel protein encoded by circGSPT1, halts GC tumorigenesis. We also provide insights into the function and underlying molecular mechanisms of GSPT1-238aa in GC and suggest that this protein represents a novel target for GC treatment.
资助项目National Natural Science Foundation of China[82173290] ; National Natural Science Foundation of China[82172946] ; National Natural Science Foundation of China[81772592] ; National Natural Science Foundation of China[81871969] ; National Natural Science Foundation of China[31601028] ; Project of Department of Education of Guangdong Province[2021KTSCX102] ; Shenzhen Basic Research Fund[JCYJ20190808163801777] ; SZU Top Ranking Project[860-00000210]
WOS研究方向Oncology
语种英语
出版者ELSEVIER IRELAND LTD
WOS记录号WOS:000831431000004
源URL[http://119.78.100.204/handle/2XEOYT63/19500]  
专题中国科学院计算技术研究所期刊论文_英文
通讯作者Zhang, Xiaojing; Jin, Zhe
作者单位1.Shenzhen Sci & Technol Dev Exchange Ctr, Shenzhen Sci & Technol Bldg, Shenzhen 518055, Guangdong, Peoples R China
2.Sidney Ki mel Comprehens Canc Ctr, Baltimore, MD 21287 USA
3.Shenzhen Univ, Sch Med, Dept Pathol, Guangdong Prov Key Lab Genome Stabil & Dis Prevent, Xueyuan Ave,Nanshan, Shenzhen 518060, Guangdong, Peoples R China
4.Shenzhen Univ, Dept Pathol, Guangdong Prov Key Lab Genome Stabil & Dis Prevent, Sch Med, Shenzhen 518060, Guangdong, Peoples R China
5.Howard Univ, Coll Med, Dept Med, Washington, DC 20060 USA
6.Howard Univ, Coll Med, Canc Ctr, Washington, DC 20060 USA
7.Meharry Med Ctr, Dept Med, Nashville, TN 37208 USA
8.Johns Hopkins Univ Sch Med, Dept Med, GI Div, Baltimore, MD 21287 USA
9.Shenzhen Inst Adv Technol, Ctr High Performance Comp, Shenzhen 518000, Guangdong, Peoples R China
推荐引用方式
GB/T 7714		 Hu, Fan,Peng, Yin,Chang, Shanshan,et al. Vimentin binds to a novel tumor suppressor protein, GSPT1-238aa, encoded by circGSPT1 with a selective encoding priority to halt autophagy in gastric carcinoma[J]. CANCER LETTERS,2022,545:14.
APA Hu, Fan.,Peng, Yin.,Chang, Shanshan.,Luo, Xiaonuan.,Yuan, Yuan.,...&Jin, Zhe.(2022).Vimentin binds to a novel tumor suppressor protein, GSPT1-238aa, encoded by circGSPT1 with a selective encoding priority to halt autophagy in gastric carcinoma.CANCER LETTERS,545,14.
MLA Hu, Fan,et al."Vimentin binds to a novel tumor suppressor protein, GSPT1-238aa, encoded by circGSPT1 with a selective encoding priority to halt autophagy in gastric carcinoma".CANCER LETTERS 545(2022):14.

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