A novel circular RNA, circXPO1, promotes lung adenocarcinoma progression by interacting with IGF2BP1
Studies have demonstrated that noncoding RNAs play important roles in various types of cancer; however, noncoding RNAs derived from regions of genomic alterations have rarely been explored, especially for circular RNAs (circRNA). Previously, we found several circRNAs were upregulated in lung adenoca...
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| Veröffentlicht in: | Cell death & disease 2020-12, Vol.11 (12), p.1031-1031, Article 1031 |
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| creator | Huang, Qi Guo, Haifa Wang, Shaodong Ma, Yi Chen, Haiming Li, Hao Li, Jiawei Li, Xiao Yang, Fan Qiu, Mantang Zhao, Song Wang, Jun |
| description | Studies have demonstrated that noncoding RNAs play important roles in various types of cancer; however, noncoding RNAs derived from regions of genomic alterations have rarely been explored, especially for circular RNAs (circRNA). Previously, we found several circRNAs were upregulated in lung adenocarcinoma (LUAD) tumor tissues by RNA sequencing. Here, we characterized a novel circRNA, circXPO1, in LUAD, which is derived from a well-established cancer therapeutic target, XPO1. circXPO1, is formed by back-splicing of exon 3 and exon 4 of XPO1 gene. circXPO1 was highly expressed in LUAD tissues compared with paired adjacent non-tumor tissues, and high circXPO1 expression correlated with worse overall survival. circXPO1 expression was positively correlated with the XPO1 gene copy number. Mechanically, circXPO1 could bind with IGF2BP1 and enhance CTNNB1 mRNA stability, and subsequently promote LUAD progression. In a LUAD patient-derived xenograft model, intratumoural injection of cholesterol-conjugated siRNA specifically targeting circXPO1 efficiently suppressed tumor growth. To summary, these results suggest that circXPO1 is critical for LUAD progression and may serve as a biomarker for poor prognosis and a therapeutic target. On the other hand, the functional roles of noncoding transcripts derived from coding genes should be re-evaluated. |
| doi_str_mv | 10.1038/s41419-020-03237-8 |
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Previously, we found several circRNAs were upregulated in lung adenocarcinoma (LUAD) tumor tissues by RNA sequencing. Here, we characterized a novel circRNA, circXPO1, in LUAD, which is derived from a well-established cancer therapeutic target, XPO1. circXPO1, is formed by back-splicing of exon 3 and exon 4 of XPO1 gene. circXPO1 was highly expressed in LUAD tissues compared with paired adjacent non-tumor tissues, and high circXPO1 expression correlated with worse overall survival. circXPO1 expression was positively correlated with the XPO1 gene copy number. Mechanically, circXPO1 could bind with IGF2BP1 and enhance CTNNB1 mRNA stability, and subsequently promote LUAD progression. In a LUAD patient-derived xenograft model, intratumoural injection of cholesterol-conjugated siRNA specifically targeting circXPO1 efficiently suppressed tumor growth. To summary, these results suggest that circXPO1 is critical for LUAD progression and may serve as a biomarker for poor prognosis and a therapeutic target. On the other hand, the functional roles of noncoding transcripts derived from coding genes should be re-evaluated.</description><identifier>ISSN: 2041-4889</identifier><identifier>EISSN: 2041-4889</identifier><identifier>DOI: 10.1038/s41419-020-03237-8</identifier><identifier>PMID: 33268793</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/1 ; 13/109 ; 13/2 ; 13/44 ; 13/51 ; 13/89 ; 14/34 ; 38/23 ; 38/77 ; 38/90 ; 45/22 ; 631/337/384 ; 631/67/1612/1350 ; 64/60 ; 82/58 ; 82/80 ; 82/83 ; Adenocarcinoma ; Adenocarcinoma of Lung - genetics ; Adenocarcinoma of Lung - pathology ; Animals ; Antibodies ; beta Catenin - genetics ; Biochemistry ; Biomedical and Life Sciences ; Cell Biology ; Cell Culture ; Cell Line, Tumor ; Cell Proliferation - genetics ; Cholesterol ; Circular RNA ; Copy number ; Disease Progression ; Exportin 1 Protein ; Gene Expression Regulation, Neoplastic ; Humans ; Immunology ; Karyopherins - genetics ; Karyopherins - metabolism ; Life Sciences ; Lung cancer ; Lung Neoplasms - genetics ; Lung Neoplasms - pathology ; Medical prognosis ; Mice ; Molecular Targeted Therapy ; mRNA stability ; Neoplasm Invasiveness ; Neoplasm Staging ; Protein Binding - genetics ; Receptors, Cytoplasmic and Nuclear - genetics ; Receptors, Cytoplasmic and Nuclear - metabolism ; RNA Stability - genetics ; RNA, Circular - genetics ; RNA, Circular - metabolism ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; RNA-Binding Proteins - metabolism ; siRNA ; Survival Analysis ; Therapeutic applications ; Xenografts</subject><ispartof>Cell death & disease, 2020-12, Vol.11 (12), p.1031-1031, Article 1031</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-b335cae3be77a4878f4e1d1ebfff87305d3fefcea262288a663d2d8a8e91506a3</citedby><cites>FETCH-LOGICAL-c474t-b335cae3be77a4878f4e1d1ebfff87305d3fefcea262288a663d2d8a8e91506a3</cites><orcidid>0000-0002-0419-9139</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710735/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710735/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27903,27904,41099,42168,51555,53770,53772</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33268793$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huang, Qi</creatorcontrib><creatorcontrib>Guo, Haifa</creatorcontrib><creatorcontrib>Wang, Shaodong</creatorcontrib><creatorcontrib>Ma, Yi</creatorcontrib><creatorcontrib>Chen, Haiming</creatorcontrib><creatorcontrib>Li, Hao</creatorcontrib><creatorcontrib>Li, Jiawei</creatorcontrib><creatorcontrib>Li, Xiao</creatorcontrib><creatorcontrib>Yang, Fan</creatorcontrib><creatorcontrib>Qiu, Mantang</creatorcontrib><creatorcontrib>Zhao, Song</creatorcontrib><creatorcontrib>Wang, Jun</creatorcontrib><title>A novel circular RNA, circXPO1, promotes lung adenocarcinoma progression by interacting with IGF2BP1</title><title>Cell death & disease</title><addtitle>Cell Death Dis</addtitle><addtitle>Cell Death Dis</addtitle><description>Studies have demonstrated that noncoding RNAs play important roles in various types of cancer; however, noncoding RNAs derived from regions of genomic alterations have rarely been explored, especially for circular RNAs (circRNA). Previously, we found several circRNAs were upregulated in lung adenocarcinoma (LUAD) tumor tissues by RNA sequencing. Here, we characterized a novel circRNA, circXPO1, in LUAD, which is derived from a well-established cancer therapeutic target, XPO1. circXPO1, is formed by back-splicing of exon 3 and exon 4 of XPO1 gene. circXPO1 was highly expressed in LUAD tissues compared with paired adjacent non-tumor tissues, and high circXPO1 expression correlated with worse overall survival. circXPO1 expression was positively correlated with the XPO1 gene copy number. Mechanically, circXPO1 could bind with IGF2BP1 and enhance CTNNB1 mRNA stability, and subsequently promote LUAD progression. In a LUAD patient-derived xenograft model, intratumoural injection of cholesterol-conjugated siRNA specifically targeting circXPO1 efficiently suppressed tumor growth. To summary, these results suggest that circXPO1 is critical for LUAD progression and may serve as a biomarker for poor prognosis and a therapeutic target. 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genetics</topic><topic>Receptors, Cytoplasmic and Nuclear - genetics</topic><topic>Receptors, Cytoplasmic and Nuclear - metabolism</topic><topic>RNA Stability - genetics</topic><topic>RNA, Circular - genetics</topic><topic>RNA, Circular - metabolism</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>RNA-Binding Proteins - metabolism</topic><topic>siRNA</topic><topic>Survival Analysis</topic><topic>Therapeutic applications</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huang, Qi</creatorcontrib><creatorcontrib>Guo, Haifa</creatorcontrib><creatorcontrib>Wang, Shaodong</creatorcontrib><creatorcontrib>Ma, Yi</creatorcontrib><creatorcontrib>Chen, Haiming</creatorcontrib><creatorcontrib>Li, Hao</creatorcontrib><creatorcontrib>Li, Jiawei</creatorcontrib><creatorcontrib>Li, Xiao</creatorcontrib><creatorcontrib>Yang, Fan</creatorcontrib><creatorcontrib>Qiu, Mantang</creatorcontrib><creatorcontrib>Zhao, Song</creatorcontrib><creatorcontrib>Wang, Jun</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell death & disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huang, Qi</au><au>Guo, Haifa</au><au>Wang, Shaodong</au><au>Ma, Yi</au><au>Chen, Haiming</au><au>Li, Hao</au><au>Li, Jiawei</au><au>Li, Xiao</au><au>Yang, Fan</au><au>Qiu, Mantang</au><au>Zhao, Song</au><au>Wang, Jun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A novel circular RNA, circXPO1, promotes lung adenocarcinoma progression by interacting with IGF2BP1</atitle><jtitle>Cell death & disease</jtitle><stitle>Cell Death Dis</stitle><addtitle>Cell Death Dis</addtitle><date>2020-12-02</date><risdate>2020</risdate><volume>11</volume><issue>12</issue><spage>1031</spage><epage>1031</epage><pages>1031-1031</pages><artnum>1031</artnum><issn>2041-4889</issn><eissn>2041-4889</eissn><abstract>Studies have demonstrated that noncoding RNAs play important roles in various types of cancer; however, noncoding RNAs derived from regions of genomic alterations have rarely been explored, especially for circular RNAs (circRNA). Previously, we found several circRNAs were upregulated in lung adenocarcinoma (LUAD) tumor tissues by RNA sequencing. Here, we characterized a novel circRNA, circXPO1, in LUAD, which is derived from a well-established cancer therapeutic target, XPO1. circXPO1, is formed by back-splicing of exon 3 and exon 4 of XPO1 gene. circXPO1 was highly expressed in LUAD tissues compared with paired adjacent non-tumor tissues, and high circXPO1 expression correlated with worse overall survival. circXPO1 expression was positively correlated with the XPO1 gene copy number. Mechanically, circXPO1 could bind with IGF2BP1 and enhance CTNNB1 mRNA stability, and subsequently promote LUAD progression. In a LUAD patient-derived xenograft model, intratumoural injection of cholesterol-conjugated siRNA specifically targeting circXPO1 efficiently suppressed tumor growth. To summary, these results suggest that circXPO1 is critical for LUAD progression and may serve as a biomarker for poor prognosis and a therapeutic target. On the other hand, the functional roles of noncoding transcripts derived from coding genes should be re-evaluated.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>33268793</pmid><doi>10.1038/s41419-020-03237-8</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-0419-9139</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 13/1 13/109 13/2 13/44 13/51 13/89 14/34 38/23 38/77 38/90 45/22 631/337/384 631/67/1612/1350 64/60 82/58 82/80 82/83 Adenocarcinoma Adenocarcinoma of Lung - genetics Adenocarcinoma of Lung - pathology Animals Antibodies beta Catenin - genetics Biochemistry Biomedical and Life Sciences Cell Biology Cell Culture Cell Line, Tumor Cell Proliferation - genetics Cholesterol Circular RNA Copy number Disease Progression Exportin 1 Protein Gene Expression Regulation, Neoplastic Humans Immunology Karyopherins - genetics Karyopherins - metabolism Life Sciences Lung cancer Lung Neoplasms - genetics Lung Neoplasms - pathology Medical prognosis Mice Molecular Targeted Therapy mRNA stability Neoplasm Invasiveness Neoplasm Staging Protein Binding - genetics Receptors, Cytoplasmic and Nuclear - genetics Receptors, Cytoplasmic and Nuclear - metabolism RNA Stability - genetics RNA, Circular - genetics RNA, Circular - metabolism RNA, Messenger - genetics RNA, Messenger - metabolism RNA-Binding Proteins - metabolism siRNA Survival Analysis Therapeutic applications Xenografts |
| title | A novel circular RNA, circXPO1, promotes lung adenocarcinoma progression by interacting with IGF2BP1 |
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