circVAMP3 Drives CAPRIN1 Phase Separation and Inhibits Hepatocellular Carcinoma by Suppressing c‐Myc Translation

Previous studies have identified the regulatory roles of circular RNAs (circRNAs) in human cancers. However, the molecular mechanisms of circRNAs in hepatocellular carcinoma (HCC) remain largely unknown. This study screens the expression profile of circRNAs in HCC and identifies circVAMP3 as a signi...

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Veröffentlicht in:Advanced science 2022-03, Vol.9 (8), p.e2103817-n/a
Hauptverfasser: Chen, Shuai, Cao, Xiaofei, Zhang, Jinyang, Wu, Wanying, Zhang, Bing, Zhao, Fangqing
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container_issue 8
container_start_page e2103817
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Cao, Xiaofei
Zhang, Jinyang
Wu, Wanying
Zhang, Bing
Zhao, Fangqing
description Previous studies have identified the regulatory roles of circular RNAs (circRNAs) in human cancers. However, the molecular mechanisms of circRNAs in hepatocellular carcinoma (HCC) remain largely unknown. This study screens the expression profile of circRNAs in HCC and identifies circVAMP3 as a significantly downregulated circRNA in HCC tissues. HCC patients with low circVAMP3 expression present poor prognosis. circVAMP3 negatively regulates the proliferation and metastasis of HCC cells in vitro and in vivo by driving phase separation of CAPRIN1 and promoting stress granule formation in cells, which can downregulate the protein level of Myc proto‐oncogene protein by inhibiting c‐Myc translation. Furthermore, circVAMP3 is widely expressed in many human tissues and is downregulated in related cancers. Therefore, circVAMP3 is a potential prognostic indicator for HCC and may serve as a therapeutic target for HCC treatment. A circular RNA, circVAMP3, is characterized here which is downregulated in hepatocellular carcinoma and other tumors. circVAMP3 interacts with CAPRIN1 and G3BP1 to trigger phase separation of CAPRIN1 and promote stress granule formation in cells by acting as a molecular scaffolder. Through stress granules, circVAMP3 exerts its tumor suppressor properties by inhibiting translation of c‐Myc.
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However, the molecular mechanisms of circRNAs in hepatocellular carcinoma (HCC) remain largely unknown. This study screens the expression profile of circRNAs in HCC and identifies circVAMP3 as a significantly downregulated circRNA in HCC tissues. HCC patients with low circVAMP3 expression present poor prognosis. circVAMP3 negatively regulates the proliferation and metastasis of HCC cells in vitro and in vivo by driving phase separation of CAPRIN1 and promoting stress granule formation in cells, which can downregulate the protein level of Myc proto‐oncogene protein by inhibiting c‐Myc translation. Furthermore, circVAMP3 is widely expressed in many human tissues and is downregulated in related cancers. Therefore, circVAMP3 is a potential prognostic indicator for HCC and may serve as a therapeutic target for HCC treatment. 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A circular RNA, circVAMP3, is characterized here which is downregulated in hepatocellular carcinoma and other tumors. circVAMP3 interacts with CAPRIN1 and G3BP1 to trigger phase separation of CAPRIN1 and promote stress granule formation in cells by acting as a molecular scaffolder. Through stress granules, circVAMP3 exerts its tumor suppressor properties by inhibiting translation of c‐Myc.</abstract><cop>Germany</cop><pub>John Wiley &amp; Sons, Inc</pub><pmid>35072355</pmid><doi>10.1002/advs.202103817</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-6216-1235</orcidid><oa>free_for_read</oa></addata></record>
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subjects CAPRIN1
Carcinoma, Hepatocellular - genetics
Cell adhesion & migration
Cell cycle
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Cell growth
circVAMP3
Gene Expression Regulation, Neoplastic - genetics
Genes
Genomes
hepatocellular carcinoma
Humans
liquid–liquid phase separation
Liver cancer
Liver Neoplasms - genetics
Medical prognosis
Metastasis
MicroRNAs
MicroRNAs - genetics
Polymerase chain reaction
RNA, Circular - genetics
Survival analysis
Tumors
title circVAMP3 Drives CAPRIN1 Phase Separation and Inhibits Hepatocellular Carcinoma by Suppressing c‐Myc Translation
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