KRAS mutations promote the intratumoral colonization of enterotoxigenic bacteroides fragilis in colorectal cancer through the regulation of the miRNA3655/SURF6/IRF7/IFNβ axis
KRAS mutations are associated with poor prognosis in colorectal cancer (CRC). Although the association between the gut microbiota and CRC has been extensively documented, it is unclear whether KRAS mutations can regulate the gut microbiota. Metagenomics has identified changes in the diversity of the...
Gespeichert in:
| Veröffentlicht in: | Gut microbes 2024-12, Vol.16 (1), p.2423043 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 1 |
| container_start_page | 2423043 |
| container_title | Gut microbes |
| container_volume | 16 |
| creator | Chen, Yizhen Liu, Shaolin Tan, Song Zheng, Yuanyuan Chen, Yifan Yang, Changshun Lin, Shengtao Mi, Yulong Li, Weihua |
| description | KRAS mutations are associated with poor prognosis in colorectal cancer (CRC). Although the association between the gut microbiota and CRC has been extensively documented, it is unclear whether KRAS mutations can regulate the gut microbiota. Metagenomics has identified changes in the diversity of the gut microbiota in CRC due to KRAS mutations. Specifically, KRAS mutations positively correlate with the abundance of the bacteroides. Understanding how to regulate the classic carcinogenic bacterium within the bacteroides, such as enterotoxigenic bacteroides fragilis (ETBF), to enhance treatment efficacy of tumors is a key focus of research. Mechanistically, we found that the reduction of miR3655 is indispensable for KRAS mutation-promoted proliferation of CRC and the abundance of ETBF. miR3655 targets SURF6 to inhibit its transcription. Further transcriptomic sequencing revealed that SURF6 promotes intratumoral colonization of ETBF in CRC by inhibiting the nuclear translocation and transcription levels of the IRF7, affecting the activation of the IFNβ promoter. Regulating miR3655 and SURF6 can promote IFNβ secretion in CRC, directly killing ETBF. These data indicate that KRAS mutations affect the intratumoral colonization of ETBF in CRC through the miR3655/SURF6/IRF7/IFNβ axis. This provides new potential strategies for treating CRC associated with KRAS mutations or high levels of ETBF. |
| doi_str_mv | 10.1080/19490976.2024.2423043 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11556274</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_6a41568b7f064e5cbb35da1a4cb28dc0</doaj_id><sourcerecordid>3128748266</sourcerecordid><originalsourceid>FETCH-LOGICAL-c413t-827399f292c95d1bc5d24d15bebb6ff6df418e2888d296d0ef2928f1224f75ba3</originalsourceid><addsrcrecordid>eNp9ks1uEzEUhUcIRKvSRwDNkk0S_49nBVVFIKIqUkrXln8nrmbGwfZAy0sh8SA8EzNJGtEN3tg6Pve7V_YpitcQzCHgYAFrUoO6YnMEEJkjgjAg-FlxOukzUHPy_Hiu2ElxntIdGBchFWD4ZXGCa4owodVp8evz-uKm7IYssw99KrcxdCHbMm9s6fscZR66EGVb6tCG3v_c2crgSttnG0MO976xvdelknoSvLGpdFE2vvVpJOzqotV5Qshe2ziiYxiaza5FtM3QHpmT0vn19QVmlC5ubtdLtlitl9Vitbz-87uU9z69Kl442SZ7ftjPitvlh6-Xn2ZXXz6uLi-uZppAnGccVbiuHaqRrqmBSlODiIFUWaWYc8w4ArlFnHODamaAnazcQYSIq6iS-KxY7bkmyDuxjb6T8UEE6cVOCLERMmavWyuYJJAyrioHGLFUK4WpkVASrRA3Goysd3vWdlCdNdpO79o-gT696f1GNOG7gJBShioyEt4eCDF8G2zKovNJ27aVvQ1DEhgiXhGOGButdG_VMaQUrTv2gUBM4RGP4RFTeMQhPGPdm3-HPFY9RmU0vN8bfO9C7OSPEFsjsnwY_3f88F77aY7_9vgLq8LX1Q</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3128748266</pqid></control><display><type>article</type><title>KRAS mutations promote the intratumoral colonization of enterotoxigenic bacteroides fragilis in colorectal cancer through the regulation of the miRNA3655/SURF6/IRF7/IFNβ axis</title><source>Taylor & Francis Open Access</source><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Chen, Yizhen ; Liu, Shaolin ; Tan, Song ; Zheng, Yuanyuan ; Chen, Yifan ; Yang, Changshun ; Lin, Shengtao ; Mi, Yulong ; Li, Weihua</creator><creatorcontrib>Chen, Yizhen ; Liu, Shaolin ; Tan, Song ; Zheng, Yuanyuan ; Chen, Yifan ; Yang, Changshun ; Lin, Shengtao ; Mi, Yulong ; Li, Weihua</creatorcontrib><description>KRAS mutations are associated with poor prognosis in colorectal cancer (CRC). Although the association between the gut microbiota and CRC has been extensively documented, it is unclear whether KRAS mutations can regulate the gut microbiota. Metagenomics has identified changes in the diversity of the gut microbiota in CRC due to KRAS mutations. Specifically, KRAS mutations positively correlate with the abundance of the bacteroides. Understanding how to regulate the classic carcinogenic bacterium within the bacteroides, such as enterotoxigenic bacteroides fragilis (ETBF), to enhance treatment efficacy of tumors is a key focus of research. Mechanistically, we found that the reduction of miR3655 is indispensable for KRAS mutation-promoted proliferation of CRC and the abundance of ETBF. miR3655 targets SURF6 to inhibit its transcription. Further transcriptomic sequencing revealed that SURF6 promotes intratumoral colonization of ETBF in CRC by inhibiting the nuclear translocation and transcription levels of the IRF7, affecting the activation of the IFNβ promoter. Regulating miR3655 and SURF6 can promote IFNβ secretion in CRC, directly killing ETBF. These data indicate that KRAS mutations affect the intratumoral colonization of ETBF in CRC through the miR3655/SURF6/IRF7/IFNβ axis. This provides new potential strategies for treating CRC associated with KRAS mutations or high levels of ETBF.</description><identifier>ISSN: 1949-0976</identifier><identifier>ISSN: 1949-0984</identifier><identifier>EISSN: 1949-0984</identifier><identifier>DOI: 10.1080/19490976.2024.2423043</identifier><identifier>PMID: 39523457</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>Animals ; Bacteroides fragilis - genetics ; Bacteroides fragilis - metabolism ; Cell Line, Tumor ; colonization ; Colorectal cancer ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - metabolism ; Colorectal Neoplasms - microbiology ; Colorectal Neoplasms - pathology ; enterotoxigenic bacteroides fragilis ; Female ; Gastrointestinal Microbiome ; Gene Expression Regulation, Neoplastic ; Humans ; Interferon Regulatory Factor-7 - genetics ; Interferon Regulatory Factor-7 - metabolism ; Interferon-beta - genetics ; Interferon-beta - metabolism ; intratumoural microbiota ; KRAS ; Mice ; Mice, Nude ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Mutation ; Proto-Oncogene Proteins p21(ras) - genetics ; Proto-Oncogene Proteins p21(ras) - metabolism ; tumor microenvironment</subject><ispartof>Gut microbes, 2024-12, Vol.16 (1), p.2423043</ispartof><rights>2024 The Author(s). Published with license by Taylor & Francis Group, LLC. 2024</rights><rights>2024 The Author(s). Published with license by Taylor & Francis Group, LLC. 2024 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c413t-827399f292c95d1bc5d24d15bebb6ff6df418e2888d296d0ef2928f1224f75ba3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556274/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556274/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2101,27501,27923,27924,53790,53792,59142,59143</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39523457$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Yizhen</creatorcontrib><creatorcontrib>Liu, Shaolin</creatorcontrib><creatorcontrib>Tan, Song</creatorcontrib><creatorcontrib>Zheng, Yuanyuan</creatorcontrib><creatorcontrib>Chen, Yifan</creatorcontrib><creatorcontrib>Yang, Changshun</creatorcontrib><creatorcontrib>Lin, Shengtao</creatorcontrib><creatorcontrib>Mi, Yulong</creatorcontrib><creatorcontrib>Li, Weihua</creatorcontrib><title>KRAS mutations promote the intratumoral colonization of enterotoxigenic bacteroides fragilis in colorectal cancer through the regulation of the miRNA3655/SURF6/IRF7/IFNβ axis</title><title>Gut microbes</title><addtitle>Gut Microbes</addtitle><description>KRAS mutations are associated with poor prognosis in colorectal cancer (CRC). Although the association between the gut microbiota and CRC has been extensively documented, it is unclear whether KRAS mutations can regulate the gut microbiota. Metagenomics has identified changes in the diversity of the gut microbiota in CRC due to KRAS mutations. Specifically, KRAS mutations positively correlate with the abundance of the bacteroides. Understanding how to regulate the classic carcinogenic bacterium within the bacteroides, such as enterotoxigenic bacteroides fragilis (ETBF), to enhance treatment efficacy of tumors is a key focus of research. Mechanistically, we found that the reduction of miR3655 is indispensable for KRAS mutation-promoted proliferation of CRC and the abundance of ETBF. miR3655 targets SURF6 to inhibit its transcription. Further transcriptomic sequencing revealed that SURF6 promotes intratumoral colonization of ETBF in CRC by inhibiting the nuclear translocation and transcription levels of the IRF7, affecting the activation of the IFNβ promoter. Regulating miR3655 and SURF6 can promote IFNβ secretion in CRC, directly killing ETBF. These data indicate that KRAS mutations affect the intratumoral colonization of ETBF in CRC through the miR3655/SURF6/IRF7/IFNβ axis. This provides new potential strategies for treating CRC associated with KRAS mutations or high levels of ETBF.</description><subject>Animals</subject><subject>Bacteroides fragilis - genetics</subject><subject>Bacteroides fragilis - metabolism</subject><subject>Cell Line, Tumor</subject><subject>colonization</subject><subject>Colorectal cancer</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Colorectal Neoplasms - microbiology</subject><subject>Colorectal Neoplasms - pathology</subject><subject>enterotoxigenic bacteroides fragilis</subject><subject>Female</subject><subject>Gastrointestinal Microbiome</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Interferon Regulatory Factor-7 - genetics</subject><subject>Interferon Regulatory Factor-7 - metabolism</subject><subject>Interferon-beta - genetics</subject><subject>Interferon-beta - metabolism</subject><subject>intratumoural microbiota</subject><subject>KRAS</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Mutation</subject><subject>Proto-Oncogene Proteins p21(ras) - genetics</subject><subject>Proto-Oncogene Proteins p21(ras) - metabolism</subject><subject>tumor microenvironment</subject><issn>1949-0976</issn><issn>1949-0984</issn><issn>1949-0984</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>0YH</sourceid><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNp9ks1uEzEUhUcIRKvSRwDNkk0S_49nBVVFIKIqUkrXln8nrmbGwfZAy0sh8SA8EzNJGtEN3tg6Pve7V_YpitcQzCHgYAFrUoO6YnMEEJkjgjAg-FlxOukzUHPy_Hiu2ElxntIdGBchFWD4ZXGCa4owodVp8evz-uKm7IYssw99KrcxdCHbMm9s6fscZR66EGVb6tCG3v_c2crgSttnG0MO976xvdelknoSvLGpdFE2vvVpJOzqotV5Qshe2ziiYxiaza5FtM3QHpmT0vn19QVmlC5ubtdLtlitl9Vitbz-87uU9z69Kl442SZ7ftjPitvlh6-Xn2ZXXz6uLi-uZppAnGccVbiuHaqRrqmBSlODiIFUWaWYc8w4ArlFnHODamaAnazcQYSIq6iS-KxY7bkmyDuxjb6T8UEE6cVOCLERMmavWyuYJJAyrioHGLFUK4WpkVASrRA3Goysd3vWdlCdNdpO79o-gT696f1GNOG7gJBShioyEt4eCDF8G2zKovNJ27aVvQ1DEhgiXhGOGButdG_VMaQUrTv2gUBM4RGP4RFTeMQhPGPdm3-HPFY9RmU0vN8bfO9C7OSPEFsjsnwY_3f88F77aY7_9vgLq8LX1Q</recordid><startdate>20241231</startdate><enddate>20241231</enddate><creator>Chen, Yizhen</creator><creator>Liu, Shaolin</creator><creator>Tan, Song</creator><creator>Zheng, Yuanyuan</creator><creator>Chen, Yifan</creator><creator>Yang, Changshun</creator><creator>Lin, Shengtao</creator><creator>Mi, Yulong</creator><creator>Li, Weihua</creator><general>Taylor & Francis</general><general>Taylor & Francis Group</general><scope>0YH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20241231</creationdate><title>KRAS mutations promote the intratumoral colonization of enterotoxigenic bacteroides fragilis in colorectal cancer through the regulation of the miRNA3655/SURF6/IRF7/IFNβ axis</title><author>Chen, Yizhen ; Liu, Shaolin ; Tan, Song ; Zheng, Yuanyuan ; Chen, Yifan ; Yang, Changshun ; Lin, Shengtao ; Mi, Yulong ; Li, Weihua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c413t-827399f292c95d1bc5d24d15bebb6ff6df418e2888d296d0ef2928f1224f75ba3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animals</topic><topic>Bacteroides fragilis - genetics</topic><topic>Bacteroides fragilis - metabolism</topic><topic>Cell Line, Tumor</topic><topic>colonization</topic><topic>Colorectal cancer</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - metabolism</topic><topic>Colorectal Neoplasms - microbiology</topic><topic>Colorectal Neoplasms - pathology</topic><topic>enterotoxigenic bacteroides fragilis</topic><topic>Female</topic><topic>Gastrointestinal Microbiome</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Interferon Regulatory Factor-7 - genetics</topic><topic>Interferon Regulatory Factor-7 - metabolism</topic><topic>Interferon-beta - genetics</topic><topic>Interferon-beta - metabolism</topic><topic>intratumoural microbiota</topic><topic>KRAS</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Mutation</topic><topic>Proto-Oncogene Proteins p21(ras) - genetics</topic><topic>Proto-Oncogene Proteins p21(ras) - metabolism</topic><topic>tumor microenvironment</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Yizhen</creatorcontrib><creatorcontrib>Liu, Shaolin</creatorcontrib><creatorcontrib>Tan, Song</creatorcontrib><creatorcontrib>Zheng, Yuanyuan</creatorcontrib><creatorcontrib>Chen, Yifan</creatorcontrib><creatorcontrib>Yang, Changshun</creatorcontrib><creatorcontrib>Lin, Shengtao</creatorcontrib><creatorcontrib>Mi, Yulong</creatorcontrib><creatorcontrib>Li, Weihua</creatorcontrib><collection>Taylor & Francis Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Gut microbes</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Yizhen</au><au>Liu, Shaolin</au><au>Tan, Song</au><au>Zheng, Yuanyuan</au><au>Chen, Yifan</au><au>Yang, Changshun</au><au>Lin, Shengtao</au><au>Mi, Yulong</au><au>Li, Weihua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>KRAS mutations promote the intratumoral colonization of enterotoxigenic bacteroides fragilis in colorectal cancer through the regulation of the miRNA3655/SURF6/IRF7/IFNβ axis</atitle><jtitle>Gut microbes</jtitle><addtitle>Gut Microbes</addtitle><date>2024-12-31</date><risdate>2024</risdate><volume>16</volume><issue>1</issue><spage>2423043</spage><pages>2423043-</pages><issn>1949-0976</issn><issn>1949-0984</issn><eissn>1949-0984</eissn><abstract>KRAS mutations are associated with poor prognosis in colorectal cancer (CRC). Although the association between the gut microbiota and CRC has been extensively documented, it is unclear whether KRAS mutations can regulate the gut microbiota. Metagenomics has identified changes in the diversity of the gut microbiota in CRC due to KRAS mutations. Specifically, KRAS mutations positively correlate with the abundance of the bacteroides. Understanding how to regulate the classic carcinogenic bacterium within the bacteroides, such as enterotoxigenic bacteroides fragilis (ETBF), to enhance treatment efficacy of tumors is a key focus of research. Mechanistically, we found that the reduction of miR3655 is indispensable for KRAS mutation-promoted proliferation of CRC and the abundance of ETBF. miR3655 targets SURF6 to inhibit its transcription. Further transcriptomic sequencing revealed that SURF6 promotes intratumoral colonization of ETBF in CRC by inhibiting the nuclear translocation and transcription levels of the IRF7, affecting the activation of the IFNβ promoter. Regulating miR3655 and SURF6 can promote IFNβ secretion in CRC, directly killing ETBF. These data indicate that KRAS mutations affect the intratumoral colonization of ETBF in CRC through the miR3655/SURF6/IRF7/IFNβ axis. This provides new potential strategies for treating CRC associated with KRAS mutations or high levels of ETBF.</abstract><cop>United States</cop><pub>Taylor & Francis</pub><pmid>39523457</pmid><doi>10.1080/19490976.2024.2423043</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1949-0976 |
| ispartof | Gut microbes, 2024-12, Vol.16 (1), p.2423043 |
| issn | 1949-0976 1949-0984 1949-0984 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11556274 |
| source | Taylor & Francis Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Animals Bacteroides fragilis - genetics Bacteroides fragilis - metabolism Cell Line, Tumor colonization Colorectal cancer Colorectal Neoplasms - genetics Colorectal Neoplasms - metabolism Colorectal Neoplasms - microbiology Colorectal Neoplasms - pathology enterotoxigenic bacteroides fragilis Female Gastrointestinal Microbiome Gene Expression Regulation, Neoplastic Humans Interferon Regulatory Factor-7 - genetics Interferon Regulatory Factor-7 - metabolism Interferon-beta - genetics Interferon-beta - metabolism intratumoural microbiota KRAS Mice Mice, Nude MicroRNAs - genetics MicroRNAs - metabolism Mutation Proto-Oncogene Proteins p21(ras) - genetics Proto-Oncogene Proteins p21(ras) - metabolism tumor microenvironment |
| title | KRAS mutations promote the intratumoral colonization of enterotoxigenic bacteroides fragilis in colorectal cancer through the regulation of the miRNA3655/SURF6/IRF7/IFNβ axis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T12%3A26%3A23IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=KRAS%20mutations%20promote%20the%20intratumoral%20colonization%20of%20enterotoxigenic%20bacteroides%20fragilis%20in%20colorectal%20cancer%20through%20the%20regulation%20of%20the%20miRNA3655/SURF6/IRF7/IFN%CE%B2%20axis&rft.jtitle=Gut%20microbes&rft.au=Chen,%20Yizhen&rft.date=2024-12-31&rft.volume=16&rft.issue=1&rft.spage=2423043&rft.pages=2423043-&rft.issn=1949-0976&rft.eissn=1949-0984&rft_id=info:doi/10.1080/19490976.2024.2423043&rft_dat=%3Cproquest_pubme%3E3128748266%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3128748266&rft_id=info:pmid/39523457&rft_doaj_id=oai_doaj_org_article_6a41568b7f064e5cbb35da1a4cb28dc0&rfr_iscdi=true |