Downregulation of TEX11 promotes S-Phase progression and proliferation in colorectal cancer cells through the FOXO3a/COP1/c-Jun/p21 axis
Colorectal cancer (CRC) is the most common digestive tract malignancy, attributing to approximately 9.4% of global cancer-related deaths. However, the pathogenesis of CRC is poorly understood. The testis-expressed 11 (TEX11) gene is located on the X chromosome and is required for spermatogenesis, an...
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| Veröffentlicht in: | Oncogene 2022-11, Vol.41 (47), p.5133-5145 |
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| creator | Zhang, Xiaodong Hu, Fangyu Zhu, Baiwang Jiao, Xueli Li, Yun Wu, Shuang Ren, Ganglin Li, Jizhen Xie, Qipeng Pan, Yifei Li, Hongyan Zhao, Lingling |
| description | Colorectal cancer (CRC) is the most common digestive tract malignancy, attributing to approximately 9.4% of global cancer-related deaths. However, the pathogenesis of CRC is poorly understood. The testis-expressed 11 (TEX11) gene is located on the X chromosome and is required for spermatogenesis, and is reported might serve as a biomarker for early onset CRC according to database analysis. However, the role played by TEX11 in cancer progression remains to be investigated. In this study, we show that TEX11 expression is significantly downregulated in CRC cell lines and clinical CRC tissue samples, and TEX11 expression correlates with poor prognosis in CRC patients. We further demonstrate that TEX11 can significantly inhibit the proliferative capacity of CRC cells in vitro and in vivo. Mechanistically, we demonstrate that TEX11 promotes transcription of COP1 by upregulating FOXO3a expression. This enhanced COP1 expression subsequently accelerates the degradation of the negative transcriptional regulator c-Jun, which, in turn, enhances p21 transcription inhibiting CRC cell cycle progression and proliferation. Overall, our findings suggest that TEX11 may be a valuable therapeutic target for the treatment of CRC. |
| doi_str_mv | 10.1038/s41388-022-02490-9 |
| format | Article |
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However, the pathogenesis of CRC is poorly understood. The testis-expressed 11 (TEX11) gene is located on the X chromosome and is required for spermatogenesis, and is reported might serve as a biomarker for early onset CRC according to database analysis. However, the role played by TEX11 in cancer progression remains to be investigated. In this study, we show that TEX11 expression is significantly downregulated in CRC cell lines and clinical CRC tissue samples, and TEX11 expression correlates with poor prognosis in CRC patients. We further demonstrate that TEX11 can significantly inhibit the proliferative capacity of CRC cells in vitro and in vivo. Mechanistically, we demonstrate that TEX11 promotes transcription of COP1 by upregulating FOXO3a expression. This enhanced COP1 expression subsequently accelerates the degradation of the negative transcriptional regulator c-Jun, which, in turn, enhances p21 transcription inhibiting CRC cell cycle progression and proliferation. Overall, our findings suggest that TEX11 may be a valuable therapeutic target for the treatment of CRC.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/s41388-022-02490-9</identifier><identifier>PMID: 36258021</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13 ; 13/1 ; 13/31 ; 13/89 ; 13/95 ; 42 ; 631/67/1504/1885 ; 631/80/83 ; Apoptosis ; c-Jun protein ; Cancer ; Cell Biology ; Cell cycle ; Cell Cycle Proteins - genetics ; Cell Cycle Proteins - metabolism ; Cell Line, Tumor ; Cell proliferation ; Cell Proliferation - genetics ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - pathology ; Cyclin-dependent kinase inhibitor p21 ; Down-Regulation ; FOXO3 protein ; Gastrointestinal tract ; Gene Expression Regulation, Neoplastic ; Human Genetics ; Humans ; Internal Medicine ; Male ; Malignancy ; Medicine ; Medicine & Public Health ; Oncology ; Spermatogenesis ; Testis - metabolism ; Therapeutic targets ; Transcription ; Transcription factors</subject><ispartof>Oncogene, 2022-11, Vol.41 (47), p.5133-5145</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2022. The Author(s), under exclusive licence to Springer Nature Limited.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c326t-32791ea5c494582ed235f91aad353dfd3a872dd4a685500c18ec11fff3adaee93</cites><orcidid>0000-0002-8907-6495 ; 0000-0002-0000-0575 ; 0000-0002-2666-9082</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41388-022-02490-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41388-022-02490-9$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27922,27923,41486,42555,51317</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36258021$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Xiaodong</creatorcontrib><creatorcontrib>Hu, Fangyu</creatorcontrib><creatorcontrib>Zhu, Baiwang</creatorcontrib><creatorcontrib>Jiao, Xueli</creatorcontrib><creatorcontrib>Li, Yun</creatorcontrib><creatorcontrib>Wu, Shuang</creatorcontrib><creatorcontrib>Ren, Ganglin</creatorcontrib><creatorcontrib>Li, Jizhen</creatorcontrib><creatorcontrib>Xie, Qipeng</creatorcontrib><creatorcontrib>Pan, Yifei</creatorcontrib><creatorcontrib>Li, Hongyan</creatorcontrib><creatorcontrib>Zhao, Lingling</creatorcontrib><title>Downregulation of TEX11 promotes S-Phase progression and proliferation in colorectal cancer cells through the FOXO3a/COP1/c-Jun/p21 axis</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>Colorectal cancer (CRC) is the most common digestive tract malignancy, attributing to approximately 9.4% of global cancer-related deaths. However, the pathogenesis of CRC is poorly understood. The testis-expressed 11 (TEX11) gene is located on the X chromosome and is required for spermatogenesis, and is reported might serve as a biomarker for early onset CRC according to database analysis. However, the role played by TEX11 in cancer progression remains to be investigated. In this study, we show that TEX11 expression is significantly downregulated in CRC cell lines and clinical CRC tissue samples, and TEX11 expression correlates with poor prognosis in CRC patients. We further demonstrate that TEX11 can significantly inhibit the proliferative capacity of CRC cells in vitro and in vivo. Mechanistically, we demonstrate that TEX11 promotes transcription of COP1 by upregulating FOXO3a expression. This enhanced COP1 expression subsequently accelerates the degradation of the negative transcriptional regulator c-Jun, which, in turn, enhances p21 transcription inhibiting CRC cell cycle progression and proliferation. Overall, our findings suggest that TEX11 may be a valuable therapeutic target for the treatment of CRC.</description><subject>13</subject><subject>13/1</subject><subject>13/31</subject><subject>13/89</subject><subject>13/95</subject><subject>42</subject><subject>631/67/1504/1885</subject><subject>631/80/83</subject><subject>Apoptosis</subject><subject>c-Jun protein</subject><subject>Cancer</subject><subject>Cell Biology</subject><subject>Cell cycle</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - genetics</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Cyclin-dependent kinase inhibitor p21</subject><subject>Down-Regulation</subject><subject>FOXO3 protein</subject><subject>Gastrointestinal tract</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Male</subject><subject>Malignancy</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Oncology</subject><subject>Spermatogenesis</subject><subject>Testis - 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Academic</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Xiaodong</au><au>Hu, Fangyu</au><au>Zhu, Baiwang</au><au>Jiao, Xueli</au><au>Li, Yun</au><au>Wu, Shuang</au><au>Ren, Ganglin</au><au>Li, Jizhen</au><au>Xie, Qipeng</au><au>Pan, Yifei</au><au>Li, Hongyan</au><au>Zhao, Lingling</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Downregulation of TEX11 promotes S-Phase progression and proliferation in colorectal cancer cells through the FOXO3a/COP1/c-Jun/p21 axis</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2022-11-18</date><risdate>2022</risdate><volume>41</volume><issue>47</issue><spage>5133</spage><epage>5145</epage><pages>5133-5145</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><abstract>Colorectal cancer (CRC) is the most common digestive tract malignancy, attributing to approximately 9.4% of global cancer-related deaths. However, the pathogenesis of CRC is poorly understood. The testis-expressed 11 (TEX11) gene is located on the X chromosome and is required for spermatogenesis, and is reported might serve as a biomarker for early onset CRC according to database analysis. However, the role played by TEX11 in cancer progression remains to be investigated. In this study, we show that TEX11 expression is significantly downregulated in CRC cell lines and clinical CRC tissue samples, and TEX11 expression correlates with poor prognosis in CRC patients. We further demonstrate that TEX11 can significantly inhibit the proliferative capacity of CRC cells in vitro and in vivo. Mechanistically, we demonstrate that TEX11 promotes transcription of COP1 by upregulating FOXO3a expression. This enhanced COP1 expression subsequently accelerates the degradation of the negative transcriptional regulator c-Jun, which, in turn, enhances p21 transcription inhibiting CRC cell cycle progression and proliferation. Overall, our findings suggest that TEX11 may be a valuable therapeutic target for the treatment of CRC.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>36258021</pmid><doi>10.1038/s41388-022-02490-9</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-8907-6495</orcidid><orcidid>https://orcid.org/0000-0002-0000-0575</orcidid><orcidid>https://orcid.org/0000-0002-2666-9082</orcidid></addata></record> |
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| subjects | 13 13/1 13/31 13/89 13/95 42 631/67/1504/1885 631/80/83 Apoptosis c-Jun protein Cancer Cell Biology Cell cycle Cell Cycle Proteins - genetics Cell Cycle Proteins - metabolism Cell Line, Tumor Cell proliferation Cell Proliferation - genetics Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - pathology Cyclin-dependent kinase inhibitor p21 Down-Regulation FOXO3 protein Gastrointestinal tract Gene Expression Regulation, Neoplastic Human Genetics Humans Internal Medicine Male Malignancy Medicine Medicine & Public Health Oncology Spermatogenesis Testis - metabolism Therapeutic targets Transcription Transcription factors |
| title | Downregulation of TEX11 promotes S-Phase progression and proliferation in colorectal cancer cells through the FOXO3a/COP1/c-Jun/p21 axis |
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