Long Noncoding RNA p53‐Stabilizing and Activating RNA Promotes p53 Signaling by Inhibiting Heterogeneous Nuclear Ribonucleoprotein K deSUMOylation and Suppresses Hepatocellular Carcinoma
To identify hepatocellular carcinoma (HCC)‐implicated long noncoding RNAs (lncRNAs), we performed an integrative omics analysis by integrating mRNA and lncRNA expression profiles in HCC tissues. We identified a collection of candidate HCC‐implicated lncRNAs. Among them, we demonstrated that an lncRN...
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Veröffentlicht in: | Hepatology (Baltimore, Md.) Md.), 2020-01, Vol.71 (1), p.112-129 |
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creator | Qin, Geng Tu, Xinyi Li, Haibei Cao, Pengbo Chen, Xi Song, Jin Han, Hui Li, Yuanfeng Guo, Bingqian Yang, Liting Yan, Pandeng Li, Peiyao Gao, Chengming Zhang, Jinxu Yang, Ying Zheng, Jian Ju, Huai‐qiang Lu, Lei Wang, Xuan Yu, Chaohui Sun, Yi Xing, Baocai Ji, Hongzan Lin, Dongxin He, Fuchu Zhou, Gangqiao |
description | To identify hepatocellular carcinoma (HCC)‐implicated long noncoding RNAs (lncRNAs), we performed an integrative omics analysis by integrating mRNA and lncRNA expression profiles in HCC tissues. We identified a collection of candidate HCC‐implicated lncRNAs. Among them, we demonstrated that an lncRNA, which is named as p53‐stabilizing and activating RNA (PSTAR), inhibits HCC cell proliferation and tumorigenicity through inducing p53‐mediated cell cycle arrest. We further revealed that PSTAR can bind to heterogeneous nuclear ribonucleoprotein K (hnRNP K) and enhance its SUMOylation and thereby strengthen the interaction between hnRNP K and p53, which ultimately leads to the accumulation and transactivation of p53. PSTAR is down‐regulated in HCC tissues, and the low PSTAR expression predicts poor prognosis in patients with HCC, especially those with wild‐type p53. Conclusion: This study sheds light on the tumor suppressor role of lncRNA PSTAR, a modulator of the p53 pathway, in HCC. |
doi_str_mv | 10.1002/hep.30793 |
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We identified a collection of candidate HCC‐implicated lncRNAs. Among them, we demonstrated that an lncRNA, which is named as p53‐stabilizing and activating RNA (PSTAR), inhibits HCC cell proliferation and tumorigenicity through inducing p53‐mediated cell cycle arrest. We further revealed that PSTAR can bind to heterogeneous nuclear ribonucleoprotein K (hnRNP K) and enhance its SUMOylation and thereby strengthen the interaction between hnRNP K and p53, which ultimately leads to the accumulation and transactivation of p53. PSTAR is down‐regulated in HCC tissues, and the low PSTAR expression predicts poor prognosis in patients with HCC, especially those with wild‐type p53. Conclusion: This study sheds light on the tumor suppressor role of lncRNA PSTAR, a modulator of the p53 pathway, in HCC.</description><identifier>ISSN: 0270-9139</identifier><identifier>EISSN: 1527-3350</identifier><identifier>DOI: 10.1002/hep.30793</identifier><identifier>PMID: 31148184</identifier><language>eng</language><publisher>United States: Wolters Kluwer Health, Inc</publisher><subject>Cell cycle ; Cell proliferation ; Gene expression ; Hepatocellular carcinoma ; Hepatology ; Liver cancer ; mRNA ; p53 Protein ; Ribonucleoprotein K ; SUMO protein ; Tumor suppressor genes ; Tumorigenicity</subject><ispartof>Hepatology (Baltimore, Md.), 2020-01, Vol.71 (1), p.112-129</ispartof><rights>2019 by the American Association for the Study of Liver Diseases.</rights><rights>2020 by the American Association for the Study of Liver Diseases.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3533-67c8976dd620b4f9b91f202464ab7613677d85c3c07279367dbd71813807437d3</citedby><cites>FETCH-LOGICAL-c3533-67c8976dd620b4f9b91f202464ab7613677d85c3c07279367dbd71813807437d3</cites><orcidid>0000-0002-4895-5063</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fhep.30793$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fhep.30793$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31148184$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Qin, Geng</creatorcontrib><creatorcontrib>Tu, Xinyi</creatorcontrib><creatorcontrib>Li, Haibei</creatorcontrib><creatorcontrib>Cao, Pengbo</creatorcontrib><creatorcontrib>Chen, Xi</creatorcontrib><creatorcontrib>Song, Jin</creatorcontrib><creatorcontrib>Han, Hui</creatorcontrib><creatorcontrib>Li, Yuanfeng</creatorcontrib><creatorcontrib>Guo, Bingqian</creatorcontrib><creatorcontrib>Yang, Liting</creatorcontrib><creatorcontrib>Yan, Pandeng</creatorcontrib><creatorcontrib>Li, Peiyao</creatorcontrib><creatorcontrib>Gao, Chengming</creatorcontrib><creatorcontrib>Zhang, Jinxu</creatorcontrib><creatorcontrib>Yang, Ying</creatorcontrib><creatorcontrib>Zheng, Jian</creatorcontrib><creatorcontrib>Ju, Huai‐qiang</creatorcontrib><creatorcontrib>Lu, Lei</creatorcontrib><creatorcontrib>Wang, Xuan</creatorcontrib><creatorcontrib>Yu, Chaohui</creatorcontrib><creatorcontrib>Sun, Yi</creatorcontrib><creatorcontrib>Xing, Baocai</creatorcontrib><creatorcontrib>Ji, Hongzan</creatorcontrib><creatorcontrib>Lin, Dongxin</creatorcontrib><creatorcontrib>He, Fuchu</creatorcontrib><creatorcontrib>Zhou, Gangqiao</creatorcontrib><title>Long Noncoding RNA p53‐Stabilizing and Activating RNA Promotes p53 Signaling by Inhibiting Heterogeneous Nuclear Ribonucleoprotein K deSUMOylation and Suppresses Hepatocellular Carcinoma</title><title>Hepatology (Baltimore, Md.)</title><addtitle>Hepatology</addtitle><description>To identify hepatocellular carcinoma (HCC)‐implicated long noncoding RNAs (lncRNAs), we performed an integrative omics analysis by integrating mRNA and lncRNA expression profiles in HCC tissues. We identified a collection of candidate HCC‐implicated lncRNAs. Among them, we demonstrated that an lncRNA, which is named as p53‐stabilizing and activating RNA (PSTAR), inhibits HCC cell proliferation and tumorigenicity through inducing p53‐mediated cell cycle arrest. We further revealed that PSTAR can bind to heterogeneous nuclear ribonucleoprotein K (hnRNP K) and enhance its SUMOylation and thereby strengthen the interaction between hnRNP K and p53, which ultimately leads to the accumulation and transactivation of p53. PSTAR is down‐regulated in HCC tissues, and the low PSTAR expression predicts poor prognosis in patients with HCC, especially those with wild‐type p53. Conclusion: This study sheds light on the tumor suppressor role of lncRNA PSTAR, a modulator of the p53 pathway, in HCC.</description><subject>Cell cycle</subject><subject>Cell proliferation</subject><subject>Gene expression</subject><subject>Hepatocellular carcinoma</subject><subject>Hepatology</subject><subject>Liver cancer</subject><subject>mRNA</subject><subject>p53 Protein</subject><subject>Ribonucleoprotein K</subject><subject>SUMO protein</subject><subject>Tumor suppressor genes</subject><subject>Tumorigenicity</subject><issn>0270-9139</issn><issn>1527-3350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp1kc1u1DAUhS1ERYfCghdAltjQRVr_JHGyHI1Kp-p0WnXoOvLfTF05dmonoGHFI_BAPA1PUmemZYHEyle-n8-5vgeADxidYITI6b3uTihiNX0FJrggLKO0QK_BBBGGshrT-hC8jfEBIVTnpHoDDinGeYWrfAJ-L7zbwKV30iuTqtvlFHYF_fPz16rnwljzY7zlTsGp7M033r9AN8G3vtdxpOHKbBy3Y0ts4YW7N8LswLnudfAb7bQfIlwO0moe4K0R3o2170KSMA5eQqVXd1fXW5sMvNv5rYauCzrGZDHXHe-91NYONr2f8SCN8y1_Bw7W3Eb9_vk8Andfzr7O5tni-vxiNl1kkhaUZiWTVc1KpUqCRL6uRY3XBJG8zLlgJaYlY6oqJJWIkbTEkimhGK4wrRDLKVP0CHze66Z5Hwcd-6Y1cRyH7z7WEEJpVWJSFwn99A_64IeQlpMompMiyaKROt5TMvgYg143XTAtD9sGo2aMtEmRNrtIE_vxWXEQrVZ_yZcME3C6B74bq7f_V2rmZzd7ySezQ6xv</recordid><startdate>202001</startdate><enddate>202001</enddate><creator>Qin, Geng</creator><creator>Tu, Xinyi</creator><creator>Li, Haibei</creator><creator>Cao, Pengbo</creator><creator>Chen, Xi</creator><creator>Song, Jin</creator><creator>Han, Hui</creator><creator>Li, Yuanfeng</creator><creator>Guo, Bingqian</creator><creator>Yang, Liting</creator><creator>Yan, Pandeng</creator><creator>Li, Peiyao</creator><creator>Gao, Chengming</creator><creator>Zhang, Jinxu</creator><creator>Yang, Ying</creator><creator>Zheng, Jian</creator><creator>Ju, Huai‐qiang</creator><creator>Lu, Lei</creator><creator>Wang, Xuan</creator><creator>Yu, Chaohui</creator><creator>Sun, Yi</creator><creator>Xing, Baocai</creator><creator>Ji, Hongzan</creator><creator>Lin, Dongxin</creator><creator>He, Fuchu</creator><creator>Zhou, Gangqiao</creator><general>Wolters Kluwer Health, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-4895-5063</orcidid></search><sort><creationdate>202001</creationdate><title>Long Noncoding RNA p53‐Stabilizing and Activating RNA Promotes p53 Signaling by Inhibiting Heterogeneous Nuclear Ribonucleoprotein K deSUMOylation and Suppresses Hepatocellular Carcinoma</title><author>Qin, Geng ; Tu, Xinyi ; Li, Haibei ; Cao, Pengbo ; Chen, Xi ; Song, Jin ; Han, Hui ; Li, Yuanfeng ; Guo, Bingqian ; Yang, Liting ; Yan, Pandeng ; Li, Peiyao ; Gao, Chengming ; Zhang, Jinxu ; Yang, Ying ; Zheng, Jian ; Ju, Huai‐qiang ; Lu, Lei ; Wang, Xuan ; Yu, Chaohui ; Sun, Yi ; Xing, Baocai ; Ji, Hongzan ; Lin, Dongxin ; He, Fuchu ; Zhou, Gangqiao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3533-67c8976dd620b4f9b91f202464ab7613677d85c3c07279367dbd71813807437d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Cell cycle</topic><topic>Cell proliferation</topic><topic>Gene expression</topic><topic>Hepatocellular carcinoma</topic><topic>Hepatology</topic><topic>Liver cancer</topic><topic>mRNA</topic><topic>p53 Protein</topic><topic>Ribonucleoprotein K</topic><topic>SUMO protein</topic><topic>Tumor suppressor genes</topic><topic>Tumorigenicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qin, Geng</creatorcontrib><creatorcontrib>Tu, Xinyi</creatorcontrib><creatorcontrib>Li, Haibei</creatorcontrib><creatorcontrib>Cao, Pengbo</creatorcontrib><creatorcontrib>Chen, Xi</creatorcontrib><creatorcontrib>Song, Jin</creatorcontrib><creatorcontrib>Han, Hui</creatorcontrib><creatorcontrib>Li, Yuanfeng</creatorcontrib><creatorcontrib>Guo, Bingqian</creatorcontrib><creatorcontrib>Yang, Liting</creatorcontrib><creatorcontrib>Yan, Pandeng</creatorcontrib><creatorcontrib>Li, Peiyao</creatorcontrib><creatorcontrib>Gao, Chengming</creatorcontrib><creatorcontrib>Zhang, Jinxu</creatorcontrib><creatorcontrib>Yang, Ying</creatorcontrib><creatorcontrib>Zheng, Jian</creatorcontrib><creatorcontrib>Ju, Huai‐qiang</creatorcontrib><creatorcontrib>Lu, Lei</creatorcontrib><creatorcontrib>Wang, Xuan</creatorcontrib><creatorcontrib>Yu, Chaohui</creatorcontrib><creatorcontrib>Sun, Yi</creatorcontrib><creatorcontrib>Xing, Baocai</creatorcontrib><creatorcontrib>Ji, Hongzan</creatorcontrib><creatorcontrib>Lin, Dongxin</creatorcontrib><creatorcontrib>He, Fuchu</creatorcontrib><creatorcontrib>Zhou, Gangqiao</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Hepatology (Baltimore, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Qin, Geng</au><au>Tu, Xinyi</au><au>Li, Haibei</au><au>Cao, Pengbo</au><au>Chen, Xi</au><au>Song, Jin</au><au>Han, Hui</au><au>Li, Yuanfeng</au><au>Guo, Bingqian</au><au>Yang, Liting</au><au>Yan, Pandeng</au><au>Li, Peiyao</au><au>Gao, Chengming</au><au>Zhang, Jinxu</au><au>Yang, Ying</au><au>Zheng, Jian</au><au>Ju, Huai‐qiang</au><au>Lu, Lei</au><au>Wang, Xuan</au><au>Yu, Chaohui</au><au>Sun, Yi</au><au>Xing, Baocai</au><au>Ji, Hongzan</au><au>Lin, Dongxin</au><au>He, Fuchu</au><au>Zhou, Gangqiao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Long Noncoding RNA p53‐Stabilizing and Activating RNA Promotes p53 Signaling by Inhibiting Heterogeneous Nuclear Ribonucleoprotein K deSUMOylation and Suppresses Hepatocellular Carcinoma</atitle><jtitle>Hepatology (Baltimore, Md.)</jtitle><addtitle>Hepatology</addtitle><date>2020-01</date><risdate>2020</risdate><volume>71</volume><issue>1</issue><spage>112</spage><epage>129</epage><pages>112-129</pages><issn>0270-9139</issn><eissn>1527-3350</eissn><abstract>To identify hepatocellular carcinoma (HCC)‐implicated long noncoding RNAs (lncRNAs), we performed an integrative omics analysis by integrating mRNA and lncRNA expression profiles in HCC tissues. We identified a collection of candidate HCC‐implicated lncRNAs. Among them, we demonstrated that an lncRNA, which is named as p53‐stabilizing and activating RNA (PSTAR), inhibits HCC cell proliferation and tumorigenicity through inducing p53‐mediated cell cycle arrest. We further revealed that PSTAR can bind to heterogeneous nuclear ribonucleoprotein K (hnRNP K) and enhance its SUMOylation and thereby strengthen the interaction between hnRNP K and p53, which ultimately leads to the accumulation and transactivation of p53. PSTAR is down‐regulated in HCC tissues, and the low PSTAR expression predicts poor prognosis in patients with HCC, especially those with wild‐type p53. 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subjects | Cell cycle Cell proliferation Gene expression Hepatocellular carcinoma Hepatology Liver cancer mRNA p53 Protein Ribonucleoprotein K SUMO protein Tumor suppressor genes Tumorigenicity |
title | Long Noncoding RNA p53‐Stabilizing and Activating RNA Promotes p53 Signaling by Inhibiting Heterogeneous Nuclear Ribonucleoprotein K deSUMOylation and Suppresses Hepatocellular Carcinoma |
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