Targeting BRD4 attenuates the stemness and aggressiveness of ameloblastoma
Background BRD4, belonging to the bromodomain extra‐terminal (BET) protein family, plays a unique role in tumor progression. However, the potential impact of BRD4 in ameloblastoma (AM) remains largely unknown. Herein, we aimed to assess the expression and functional role of BRD4 in AM. Methods The e...
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| Veröffentlicht in: | Oral diseases 2024-07, Vol.30 (5), p.3212-3224 |
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| creator | Xie, Jiaxiang Zhang, Jingqi Xiong, Gan Ouyang, Shengqi Yun, Bokai Xu, Xiuyun Wang, Wenjin Zhang, Ming Xie, Nan Chen, Demeng Wang, Cheng |
| description | Background
BRD4, belonging to the bromodomain extra‐terminal (BET) protein family, plays a unique role in tumor progression. However, the potential impact of BRD4 in ameloblastoma (AM) remains largely unknown. Herein, we aimed to assess the expression and functional role of BRD4 in AM.
Methods
The expression level of BRD4 was assessed by immunohistochemistry. The proliferation, migration, invasion, and tumorigenic abilities of AM cells were assessed by a series of assays. To explore the molecular expression profile of BRD4‐depleted AM cells, RNA sequencing (RNA‐seq) was performed. Bioinformatic analysis was performed on AM expression matrices obtained from the Gene Expression Omnibus (GEO). The therapeutic efficacy of BET‐inhibitors (BETi) was assessed with AM patient‐derived organoids.
Results
Upregulation of BRD4 was observed in conventional AMs, recurrent AMs, and ameloblastic carcinomas. Depletion of BRD4 inhibited proliferation, invasion, migration, and tumorigenesis in AM. Administration of BETi attenuated the aggressiveness of AM and the growth of AM patient‐derived organoids. Bioinformatic analysis indicated that BRD4 may promote AM progression by regulating the Wnt pathway and stemness‐associated pathways.
Conclusion
BRD4 increases the aggressiveness and promotes the recurrence of ameloblastoma by regulating the Wnt pathway and stemness‐associated pathways. These findings highlight BRD4 as a promising therapeutic target in AM management. |
| doi_str_mv | 10.1111/odi.14762 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2874261054</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2874261054</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3532-9ef73e6047fd4b51c9eddd623b493e133b157d037def9573e5c26a761158d1993</originalsourceid><addsrcrecordid>eNp1kMtKw0AUhgdRbK0ufAEJuNFF2rlkZjpLbb1UCgWp4G6YZE5qSi41kyh9e8emuhA8m_Nz-Pg5fAidEzwkfkaVzYYkkoIeoD4RmIR4TPmhz4xHIafstYdOnFtjTKRi9Bj1mJRqrKjoo6elqVfQZOUquH2eRoFpGihb04ALmjcIXANFCc4FprSBWa1qn7MP2J2qNDAF5FWcG9dUhTlFR6nJHZzt9wC93N8tJ4_hfPEwm9zMw4RxRkMFqWQgcCRTG8WcJAqstYKyOFIMCGMx4dJiJi2kinuUJ1QYKQjhY0uUYgN01fVu6uq9BdfoInMJ5LkpoWqdpmMZUUEwjzx6-QddV21d-u80846kkFhRT113VFJXztWQ6k2dFabeaoL1t2DtBeudYM9e7BvbuAD7S_4Y9cCoAz6zHLb_N-nFdNZVfgEBpINr</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3082767092</pqid></control><display><type>article</type><title>Targeting BRD4 attenuates the stemness and aggressiveness of ameloblastoma</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><creator>Xie, Jiaxiang ; Zhang, Jingqi ; Xiong, Gan ; Ouyang, Shengqi ; Yun, Bokai ; Xu, Xiuyun ; Wang, Wenjin ; Zhang, Ming ; Xie, Nan ; Chen, Demeng ; Wang, Cheng</creator><creatorcontrib>Xie, Jiaxiang ; Zhang, Jingqi ; Xiong, Gan ; Ouyang, Shengqi ; Yun, Bokai ; Xu, Xiuyun ; Wang, Wenjin ; Zhang, Ming ; Xie, Nan ; Chen, Demeng ; Wang, Cheng</creatorcontrib><description>Background
BRD4, belonging to the bromodomain extra‐terminal (BET) protein family, plays a unique role in tumor progression. However, the potential impact of BRD4 in ameloblastoma (AM) remains largely unknown. Herein, we aimed to assess the expression and functional role of BRD4 in AM.
Methods
The expression level of BRD4 was assessed by immunohistochemistry. The proliferation, migration, invasion, and tumorigenic abilities of AM cells were assessed by a series of assays. To explore the molecular expression profile of BRD4‐depleted AM cells, RNA sequencing (RNA‐seq) was performed. Bioinformatic analysis was performed on AM expression matrices obtained from the Gene Expression Omnibus (GEO). The therapeutic efficacy of BET‐inhibitors (BETi) was assessed with AM patient‐derived organoids.
Results
Upregulation of BRD4 was observed in conventional AMs, recurrent AMs, and ameloblastic carcinomas. Depletion of BRD4 inhibited proliferation, invasion, migration, and tumorigenesis in AM. Administration of BETi attenuated the aggressiveness of AM and the growth of AM patient‐derived organoids. Bioinformatic analysis indicated that BRD4 may promote AM progression by regulating the Wnt pathway and stemness‐associated pathways.
Conclusion
BRD4 increases the aggressiveness and promotes the recurrence of ameloblastoma by regulating the Wnt pathway and stemness‐associated pathways. These findings highlight BRD4 as a promising therapeutic target in AM management.</description><identifier>ISSN: 1354-523X</identifier><identifier>ISSN: 1601-0825</identifier><identifier>EISSN: 1601-0825</identifier><identifier>DOI: 10.1111/odi.14762</identifier><identifier>PMID: 37798926</identifier><language>eng</language><publisher>Denmark: Wiley Subscription Services, Inc</publisher><subject>Ameloblastoma ; Ameloblastoma - genetics ; Ameloblastoma - metabolism ; Ameloblastoma - pathology ; Analysis ; Animals ; BRD4 ; Bromodomain Containing Proteins ; Carcinogenesis - genetics ; Cell Cycle Proteins - genetics ; Cell Cycle Proteins - metabolism ; Cell Line, Tumor ; Cell migration ; Cell Movement ; Cell proliferation ; Cell Proliferation - drug effects ; Female ; Gene expression ; Humans ; Immunohistochemistry ; Jaw Neoplasms - genetics ; Jaw Neoplasms - metabolism ; Jaw Neoplasms - pathology ; Male ; Mandibular Neoplasms - genetics ; Mandibular Neoplasms - metabolism ; Mandibular Neoplasms - pathology ; Mice ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local - pathology ; Neoplastic Stem Cells - drug effects ; Neoplastic Stem Cells - metabolism ; Neoplastic Stem Cells - pathology ; Organoids ; Proteins ; Therapeutic targets ; Transcription Factors - genetics ; Tumorigenesis ; Up-Regulation ; Wnt pathway ; Wnt protein ; Wnt Signaling Pathway</subject><ispartof>Oral diseases, 2024-07, Vol.30 (5), p.3212-3224</ispartof><rights>2023 Wiley Periodicals LLC.</rights><rights>2024 Wiley Periodicals LLC.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3532-9ef73e6047fd4b51c9eddd623b493e133b157d037def9573e5c26a761158d1993</citedby><cites>FETCH-LOGICAL-c3532-9ef73e6047fd4b51c9eddd623b493e133b157d037def9573e5c26a761158d1993</cites><orcidid>0000-0001-8155-5064</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fodi.14762$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fodi.14762$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37798926$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xie, Jiaxiang</creatorcontrib><creatorcontrib>Zhang, Jingqi</creatorcontrib><creatorcontrib>Xiong, Gan</creatorcontrib><creatorcontrib>Ouyang, Shengqi</creatorcontrib><creatorcontrib>Yun, Bokai</creatorcontrib><creatorcontrib>Xu, Xiuyun</creatorcontrib><creatorcontrib>Wang, Wenjin</creatorcontrib><creatorcontrib>Zhang, Ming</creatorcontrib><creatorcontrib>Xie, Nan</creatorcontrib><creatorcontrib>Chen, Demeng</creatorcontrib><creatorcontrib>Wang, Cheng</creatorcontrib><title>Targeting BRD4 attenuates the stemness and aggressiveness of ameloblastoma</title><title>Oral diseases</title><addtitle>Oral Dis</addtitle><description>Background
BRD4, belonging to the bromodomain extra‐terminal (BET) protein family, plays a unique role in tumor progression. However, the potential impact of BRD4 in ameloblastoma (AM) remains largely unknown. Herein, we aimed to assess the expression and functional role of BRD4 in AM.
Methods
The expression level of BRD4 was assessed by immunohistochemistry. The proliferation, migration, invasion, and tumorigenic abilities of AM cells were assessed by a series of assays. To explore the molecular expression profile of BRD4‐depleted AM cells, RNA sequencing (RNA‐seq) was performed. Bioinformatic analysis was performed on AM expression matrices obtained from the Gene Expression Omnibus (GEO). The therapeutic efficacy of BET‐inhibitors (BETi) was assessed with AM patient‐derived organoids.
Results
Upregulation of BRD4 was observed in conventional AMs, recurrent AMs, and ameloblastic carcinomas. Depletion of BRD4 inhibited proliferation, invasion, migration, and tumorigenesis in AM. Administration of BETi attenuated the aggressiveness of AM and the growth of AM patient‐derived organoids. Bioinformatic analysis indicated that BRD4 may promote AM progression by regulating the Wnt pathway and stemness‐associated pathways.
Conclusion
BRD4 increases the aggressiveness and promotes the recurrence of ameloblastoma by regulating the Wnt pathway and stemness‐associated pathways. These findings highlight BRD4 as a promising therapeutic target in AM management.</description><subject>Ameloblastoma</subject><subject>Ameloblastoma - genetics</subject><subject>Ameloblastoma - metabolism</subject><subject>Ameloblastoma - pathology</subject><subject>Analysis</subject><subject>Animals</subject><subject>BRD4</subject><subject>Bromodomain Containing Proteins</subject><subject>Carcinogenesis - genetics</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Cell migration</subject><subject>Cell Movement</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Female</subject><subject>Gene expression</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Jaw Neoplasms - genetics</subject><subject>Jaw Neoplasms - metabolism</subject><subject>Jaw Neoplasms - pathology</subject><subject>Male</subject><subject>Mandibular Neoplasms - genetics</subject><subject>Mandibular Neoplasms - metabolism</subject><subject>Mandibular Neoplasms - pathology</subject><subject>Mice</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplasm Recurrence, Local - pathology</subject><subject>Neoplastic Stem Cells - drug effects</subject><subject>Neoplastic Stem Cells - metabolism</subject><subject>Neoplastic Stem Cells - pathology</subject><subject>Organoids</subject><subject>Proteins</subject><subject>Therapeutic targets</subject><subject>Transcription Factors - genetics</subject><subject>Tumorigenesis</subject><subject>Up-Regulation</subject><subject>Wnt pathway</subject><subject>Wnt protein</subject><subject>Wnt Signaling Pathway</subject><issn>1354-523X</issn><issn>1601-0825</issn><issn>1601-0825</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMtKw0AUhgdRbK0ufAEJuNFF2rlkZjpLbb1UCgWp4G6YZE5qSi41kyh9e8emuhA8m_Nz-Pg5fAidEzwkfkaVzYYkkoIeoD4RmIR4TPmhz4xHIafstYdOnFtjTKRi9Bj1mJRqrKjoo6elqVfQZOUquH2eRoFpGihb04ALmjcIXANFCc4FprSBWa1qn7MP2J2qNDAF5FWcG9dUhTlFR6nJHZzt9wC93N8tJ4_hfPEwm9zMw4RxRkMFqWQgcCRTG8WcJAqstYKyOFIMCGMx4dJiJi2kinuUJ1QYKQjhY0uUYgN01fVu6uq9BdfoInMJ5LkpoWqdpmMZUUEwjzx6-QddV21d-u80846kkFhRT113VFJXztWQ6k2dFabeaoL1t2DtBeudYM9e7BvbuAD7S_4Y9cCoAz6zHLb_N-nFdNZVfgEBpINr</recordid><startdate>202407</startdate><enddate>202407</enddate><creator>Xie, Jiaxiang</creator><creator>Zhang, Jingqi</creator><creator>Xiong, Gan</creator><creator>Ouyang, Shengqi</creator><creator>Yun, Bokai</creator><creator>Xu, Xiuyun</creator><creator>Wang, Wenjin</creator><creator>Zhang, Ming</creator><creator>Xie, Nan</creator><creator>Chen, Demeng</creator><creator>Wang, Cheng</creator><general>Wiley Subscription Services, Inc</general><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>7QP</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-8155-5064</orcidid></search><sort><creationdate>202407</creationdate><title>Targeting BRD4 attenuates the stemness and aggressiveness of ameloblastoma</title><author>Xie, Jiaxiang ; Zhang, Jingqi ; Xiong, Gan ; Ouyang, Shengqi ; Yun, Bokai ; Xu, Xiuyun ; Wang, Wenjin ; Zhang, Ming ; Xie, Nan ; Chen, Demeng ; Wang, Cheng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3532-9ef73e6047fd4b51c9eddd623b493e133b157d037def9573e5c26a761158d1993</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Ameloblastoma</topic><topic>Ameloblastoma - genetics</topic><topic>Ameloblastoma - metabolism</topic><topic>Ameloblastoma - pathology</topic><topic>Analysis</topic><topic>Animals</topic><topic>BRD4</topic><topic>Bromodomain Containing Proteins</topic><topic>Carcinogenesis - genetics</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Cell migration</topic><topic>Cell Movement</topic><topic>Cell proliferation</topic><topic>Cell Proliferation - drug effects</topic><topic>Female</topic><topic>Gene expression</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Jaw Neoplasms - genetics</topic><topic>Jaw Neoplasms - metabolism</topic><topic>Jaw Neoplasms - pathology</topic><topic>Male</topic><topic>Mandibular Neoplasms - genetics</topic><topic>Mandibular Neoplasms - metabolism</topic><topic>Mandibular Neoplasms - pathology</topic><topic>Mice</topic><topic>Neoplasm Invasiveness</topic><topic>Neoplasm Recurrence, Local - pathology</topic><topic>Neoplastic Stem Cells - drug effects</topic><topic>Neoplastic Stem Cells - metabolism</topic><topic>Neoplastic Stem Cells - pathology</topic><topic>Organoids</topic><topic>Proteins</topic><topic>Therapeutic targets</topic><topic>Transcription Factors - genetics</topic><topic>Tumorigenesis</topic><topic>Up-Regulation</topic><topic>Wnt pathway</topic><topic>Wnt protein</topic><topic>Wnt Signaling Pathway</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xie, Jiaxiang</creatorcontrib><creatorcontrib>Zhang, Jingqi</creatorcontrib><creatorcontrib>Xiong, Gan</creatorcontrib><creatorcontrib>Ouyang, Shengqi</creatorcontrib><creatorcontrib>Yun, Bokai</creatorcontrib><creatorcontrib>Xu, Xiuyun</creatorcontrib><creatorcontrib>Wang, Wenjin</creatorcontrib><creatorcontrib>Zhang, Ming</creatorcontrib><creatorcontrib>Xie, Nan</creatorcontrib><creatorcontrib>Chen, Demeng</creatorcontrib><creatorcontrib>Wang, Cheng</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Oral diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xie, Jiaxiang</au><au>Zhang, Jingqi</au><au>Xiong, Gan</au><au>Ouyang, Shengqi</au><au>Yun, Bokai</au><au>Xu, Xiuyun</au><au>Wang, Wenjin</au><au>Zhang, Ming</au><au>Xie, Nan</au><au>Chen, Demeng</au><au>Wang, Cheng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Targeting BRD4 attenuates the stemness and aggressiveness of ameloblastoma</atitle><jtitle>Oral diseases</jtitle><addtitle>Oral Dis</addtitle><date>2024-07</date><risdate>2024</risdate><volume>30</volume><issue>5</issue><spage>3212</spage><epage>3224</epage><pages>3212-3224</pages><issn>1354-523X</issn><issn>1601-0825</issn><eissn>1601-0825</eissn><abstract>Background
BRD4, belonging to the bromodomain extra‐terminal (BET) protein family, plays a unique role in tumor progression. However, the potential impact of BRD4 in ameloblastoma (AM) remains largely unknown. Herein, we aimed to assess the expression and functional role of BRD4 in AM.
Methods
The expression level of BRD4 was assessed by immunohistochemistry. The proliferation, migration, invasion, and tumorigenic abilities of AM cells were assessed by a series of assays. To explore the molecular expression profile of BRD4‐depleted AM cells, RNA sequencing (RNA‐seq) was performed. Bioinformatic analysis was performed on AM expression matrices obtained from the Gene Expression Omnibus (GEO). The therapeutic efficacy of BET‐inhibitors (BETi) was assessed with AM patient‐derived organoids.
Results
Upregulation of BRD4 was observed in conventional AMs, recurrent AMs, and ameloblastic carcinomas. Depletion of BRD4 inhibited proliferation, invasion, migration, and tumorigenesis in AM. Administration of BETi attenuated the aggressiveness of AM and the growth of AM patient‐derived organoids. Bioinformatic analysis indicated that BRD4 may promote AM progression by regulating the Wnt pathway and stemness‐associated pathways.
Conclusion
BRD4 increases the aggressiveness and promotes the recurrence of ameloblastoma by regulating the Wnt pathway and stemness‐associated pathways. These findings highlight BRD4 as a promising therapeutic target in AM management.</abstract><cop>Denmark</cop><pub>Wiley Subscription Services, Inc</pub><pmid>37798926</pmid><doi>10.1111/odi.14762</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-8155-5064</orcidid></addata></record> |
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| subjects | Ameloblastoma Ameloblastoma - genetics Ameloblastoma - metabolism Ameloblastoma - pathology Analysis Animals BRD4 Bromodomain Containing Proteins Carcinogenesis - genetics Cell Cycle Proteins - genetics Cell Cycle Proteins - metabolism Cell Line, Tumor Cell migration Cell Movement Cell proliferation Cell Proliferation - drug effects Female Gene expression Humans Immunohistochemistry Jaw Neoplasms - genetics Jaw Neoplasms - metabolism Jaw Neoplasms - pathology Male Mandibular Neoplasms - genetics Mandibular Neoplasms - metabolism Mandibular Neoplasms - pathology Mice Neoplasm Invasiveness Neoplasm Recurrence, Local - pathology Neoplastic Stem Cells - drug effects Neoplastic Stem Cells - metabolism Neoplastic Stem Cells - pathology Organoids Proteins Therapeutic targets Transcription Factors - genetics Tumorigenesis Up-Regulation Wnt pathway Wnt protein Wnt Signaling Pathway |
| title | Targeting BRD4 attenuates the stemness and aggressiveness of ameloblastoma |
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