The long noncoding RNA TUG1 regulates blood-tumor barrier permeability by targeting miR-144
Blood-tumor barrier (BTB) limits the delivery of chemotherapeutic agent to brain tumor tissues. Long non-coding RNAs (lncRNAs) have been shown to play critical regulatory roles in various biologic processes of tumors. However, the role of lncRNAs in BTB permeability is unclear. LncRNA TUG1 (taurine...
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| Veröffentlicht in: | Oncotarget 2015-08, Vol.6 (23), p.19759-19779 |
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| creator | Cai, Heng Xue, Yixue Wang, Ping Wang, Zhenhua Li, Zhen Hu, Yi Li, Zhiqing Shang, Xiuli Liu, Yunhui |
| description | Blood-tumor barrier (BTB) limits the delivery of chemotherapeutic agent to brain tumor tissues. Long non-coding RNAs (lncRNAs) have been shown to play critical regulatory roles in various biologic processes of tumors. However, the role of lncRNAs in BTB permeability is unclear. LncRNA TUG1 (taurine upregulated gene 1) was highly expressed in glioma vascular endothelial cells from glioma tissues. It also upregulated in glioma co-cultured endothelial cells (GEC) from BTB model in vitro. Knockdown of TUG1 increased BTB permeability, and meanwhile down-regulated the expression of the tight junction proteins ZO-1, occludin, and claudin-5. Both bioinformatics and luciferase reporter assays demonstrated that TUG1 influenced BTB permeability via binding to miR-144. Furthermore, Knockdown of TUG1 also down-regulated Heat shock transcription factor 2 (HSF2), a transcription factor of the heat shock transcription factor family, which was defined as a direct and functional downstream target of miR-144. HSF2 up-regulated the promoter activities and interacted with the promoters of ZO-1, occludin, and claudin-5 in GECs. In conclusion, our results indicate that knockdown of TUG1 increased BTB permeability via binding to miR-144 and then reducing EC tight junction protein expression by targeting HSF2. Thus, TUG1 may represent a useful future therapeutic target for enhancing BTB permeability. |
| doi_str_mv | 10.18632/oncotarget.4331 |
| format | Article |
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Long non-coding RNAs (lncRNAs) have been shown to play critical regulatory roles in various biologic processes of tumors. However, the role of lncRNAs in BTB permeability is unclear. LncRNA TUG1 (taurine upregulated gene 1) was highly expressed in glioma vascular endothelial cells from glioma tissues. It also upregulated in glioma co-cultured endothelial cells (GEC) from BTB model in vitro. Knockdown of TUG1 increased BTB permeability, and meanwhile down-regulated the expression of the tight junction proteins ZO-1, occludin, and claudin-5. Both bioinformatics and luciferase reporter assays demonstrated that TUG1 influenced BTB permeability via binding to miR-144. Furthermore, Knockdown of TUG1 also down-regulated Heat shock transcription factor 2 (HSF2), a transcription factor of the heat shock transcription factor family, which was defined as a direct and functional downstream target of miR-144. HSF2 up-regulated the promoter activities and interacted with the promoters of ZO-1, occludin, and claudin-5 in GECs. In conclusion, our results indicate that knockdown of TUG1 increased BTB permeability via binding to miR-144 and then reducing EC tight junction protein expression by targeting HSF2. Thus, TUG1 may represent a useful future therapeutic target for enhancing BTB permeability.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.4331</identifier><identifier>PMID: 26078353</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>3' Untranslated Regions ; Animals ; Binding Sites ; Blood-Brain Barrier - metabolism ; Blood-Brain Barrier - pathology ; Brain Neoplasms - genetics ; Brain Neoplasms - metabolism ; Brain Neoplasms - pathology ; Capillary Permeability ; Cell Line ; Claudin-5 - genetics ; Claudin-5 - metabolism ; Coculture Techniques ; Electric Impedance ; Gene Expression Regulation, Neoplastic ; Glioma - genetics ; Glioma - metabolism ; Glioma - pathology ; Heat-Shock Proteins - genetics ; Heat-Shock Proteins - metabolism ; Humans ; Male ; Mice, Inbred BALB C ; Mice, Nude ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Occludin - genetics ; Occludin - metabolism ; Research Paper ; RNA Interference ; RNA, Long Noncoding - genetics ; RNA, Long Noncoding - metabolism ; Tight Junctions - metabolism ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Transcription, Genetic ; Transfection ; Tumor Cells, Cultured ; Zonula Occludens-1 Protein - genetics ; Zonula Occludens-1 Protein - metabolism</subject><ispartof>Oncotarget, 2015-08, Vol.6 (23), p.19759-19779</ispartof><rights>Copyright: © 2015 Cai et al. 2015</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c462t-c9f1928c99a1e76d8ed2b5c4da5f9239eb233d6474c069764b3121380ffaf2923</citedby><cites>FETCH-LOGICAL-c462t-c9f1928c99a1e76d8ed2b5c4da5f9239eb233d6474c069764b3121380ffaf2923</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/PMC4637319/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4637319/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26078353$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cai, Heng</creatorcontrib><creatorcontrib>Xue, Yixue</creatorcontrib><creatorcontrib>Wang, Ping</creatorcontrib><creatorcontrib>Wang, Zhenhua</creatorcontrib><creatorcontrib>Li, Zhen</creatorcontrib><creatorcontrib>Hu, Yi</creatorcontrib><creatorcontrib>Li, Zhiqing</creatorcontrib><creatorcontrib>Shang, Xiuli</creatorcontrib><creatorcontrib>Liu, Yunhui</creatorcontrib><title>The long noncoding RNA TUG1 regulates blood-tumor barrier permeability by targeting miR-144</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>Blood-tumor barrier (BTB) limits the delivery of chemotherapeutic agent to brain tumor tissues. Long non-coding RNAs (lncRNAs) have been shown to play critical regulatory roles in various biologic processes of tumors. However, the role of lncRNAs in BTB permeability is unclear. LncRNA TUG1 (taurine upregulated gene 1) was highly expressed in glioma vascular endothelial cells from glioma tissues. It also upregulated in glioma co-cultured endothelial cells (GEC) from BTB model in vitro. Knockdown of TUG1 increased BTB permeability, and meanwhile down-regulated the expression of the tight junction proteins ZO-1, occludin, and claudin-5. Both bioinformatics and luciferase reporter assays demonstrated that TUG1 influenced BTB permeability via binding to miR-144. Furthermore, Knockdown of TUG1 also down-regulated Heat shock transcription factor 2 (HSF2), a transcription factor of the heat shock transcription factor family, which was defined as a direct and functional downstream target of miR-144. HSF2 up-regulated the promoter activities and interacted with the promoters of ZO-1, occludin, and claudin-5 in GECs. In conclusion, our results indicate that knockdown of TUG1 increased BTB permeability via binding to miR-144 and then reducing EC tight junction protein expression by targeting HSF2. Thus, TUG1 may represent a useful future therapeutic target for enhancing BTB permeability.</description><subject>3' Untranslated Regions</subject><subject>Animals</subject><subject>Binding Sites</subject><subject>Blood-Brain Barrier - metabolism</subject><subject>Blood-Brain Barrier - pathology</subject><subject>Brain Neoplasms - genetics</subject><subject>Brain Neoplasms - metabolism</subject><subject>Brain Neoplasms - pathology</subject><subject>Capillary Permeability</subject><subject>Cell Line</subject><subject>Claudin-5 - genetics</subject><subject>Claudin-5 - metabolism</subject><subject>Coculture Techniques</subject><subject>Electric Impedance</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Glioma - genetics</subject><subject>Glioma - metabolism</subject><subject>Glioma - pathology</subject><subject>Heat-Shock Proteins - genetics</subject><subject>Heat-Shock Proteins - metabolism</subject><subject>Humans</subject><subject>Male</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Occludin - genetics</subject><subject>Occludin - metabolism</subject><subject>Research Paper</subject><subject>RNA Interference</subject><subject>RNA, Long Noncoding - genetics</subject><subject>RNA, Long Noncoding - metabolism</subject><subject>Tight Junctions - metabolism</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Transcription, Genetic</subject><subject>Transfection</subject><subject>Tumor Cells, Cultured</subject><subject>Zonula Occludens-1 Protein - genetics</subject><subject>Zonula Occludens-1 Protein - metabolism</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkc1Lw0AQxRdRtNTePckevaRmP5LNXgQpWoWiUOrJw7LZTNqVJFt3E6H_vYnVqnOZgXnzmwcPoQsST0mWMnrtGuNa7dfQTjlj5AiNiOQyoknCjv_MZ2gSwlvcV8JFRuUpOqNpLDKWsBF6XW0AV65Z42bAFbaflk-3ePUyJ9jDuqt0CwHnlXNF1Ha18zjX3lvweAu-Bp3byrY7nO_w3soAqO0yIpyfo5NSVwEm332MXu7vVrOHaPE8f5zdLiLDU9pGRpZE0sxIqQmItMigoHlieKGTUlImIaeMFSkX3MSpFCnPGaGEZXFZ6pL2ijG62XO3XV5DYaBpva7U1tta-51y2qr_m8Zu1Np9KJ4ywYjsAVffAO_eOwitqm0wUFW6AdcFRUQskkQQOUjjvdR4F4KH8vCGxOorFvUbixpi6U8u_9o7HPyEwD4B7D6L9A</recordid><startdate>20150814</startdate><enddate>20150814</enddate><creator>Cai, Heng</creator><creator>Xue, Yixue</creator><creator>Wang, Ping</creator><creator>Wang, Zhenhua</creator><creator>Li, Zhen</creator><creator>Hu, Yi</creator><creator>Li, Zhiqing</creator><creator>Shang, Xiuli</creator><creator>Liu, Yunhui</creator><general>Impact Journals LLC</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150814</creationdate><title>The long noncoding RNA TUG1 regulates blood-tumor barrier permeability by targeting miR-144</title><author>Cai, Heng ; Xue, Yixue ; Wang, Ping ; Wang, Zhenhua ; Li, Zhen ; Hu, Yi ; Li, Zhiqing ; Shang, Xiuli ; Liu, Yunhui</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c462t-c9f1928c99a1e76d8ed2b5c4da5f9239eb233d6474c069764b3121380ffaf2923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>3' Untranslated Regions</topic><topic>Animals</topic><topic>Binding Sites</topic><topic>Blood-Brain Barrier - metabolism</topic><topic>Blood-Brain Barrier - pathology</topic><topic>Brain Neoplasms - genetics</topic><topic>Brain Neoplasms - metabolism</topic><topic>Brain Neoplasms - pathology</topic><topic>Capillary Permeability</topic><topic>Cell Line</topic><topic>Claudin-5 - genetics</topic><topic>Claudin-5 - metabolism</topic><topic>Coculture Techniques</topic><topic>Electric Impedance</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Glioma - genetics</topic><topic>Glioma - metabolism</topic><topic>Glioma - pathology</topic><topic>Heat-Shock Proteins - genetics</topic><topic>Heat-Shock Proteins - metabolism</topic><topic>Humans</topic><topic>Male</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Occludin - genetics</topic><topic>Occludin - metabolism</topic><topic>Research Paper</topic><topic>RNA Interference</topic><topic>RNA, Long Noncoding - genetics</topic><topic>RNA, Long Noncoding - metabolism</topic><topic>Tight Junctions - metabolism</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Transcription, Genetic</topic><topic>Transfection</topic><topic>Tumor Cells, Cultured</topic><topic>Zonula Occludens-1 Protein - genetics</topic><topic>Zonula Occludens-1 Protein - metabolism</topic><toplevel>online_resources</toplevel><creatorcontrib>Cai, Heng</creatorcontrib><creatorcontrib>Xue, Yixue</creatorcontrib><creatorcontrib>Wang, Ping</creatorcontrib><creatorcontrib>Wang, Zhenhua</creatorcontrib><creatorcontrib>Li, Zhen</creatorcontrib><creatorcontrib>Hu, Yi</creatorcontrib><creatorcontrib>Li, Zhiqing</creatorcontrib><creatorcontrib>Shang, Xiuli</creatorcontrib><creatorcontrib>Liu, Yunhui</creatorcontrib><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><jtitle>Oncotarget</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cai, Heng</au><au>Xue, Yixue</au><au>Wang, Ping</au><au>Wang, Zhenhua</au><au>Li, Zhen</au><au>Hu, Yi</au><au>Li, Zhiqing</au><au>Shang, Xiuli</au><au>Liu, Yunhui</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The long noncoding RNA TUG1 regulates blood-tumor barrier permeability by targeting miR-144</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2015-08-14</date><risdate>2015</risdate><volume>6</volume><issue>23</issue><spage>19759</spage><epage>19779</epage><pages>19759-19779</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>Blood-tumor barrier (BTB) limits the delivery of chemotherapeutic agent to brain tumor tissues. Long non-coding RNAs (lncRNAs) have been shown to play critical regulatory roles in various biologic processes of tumors. However, the role of lncRNAs in BTB permeability is unclear. LncRNA TUG1 (taurine upregulated gene 1) was highly expressed in glioma vascular endothelial cells from glioma tissues. It also upregulated in glioma co-cultured endothelial cells (GEC) from BTB model in vitro. Knockdown of TUG1 increased BTB permeability, and meanwhile down-regulated the expression of the tight junction proteins ZO-1, occludin, and claudin-5. Both bioinformatics and luciferase reporter assays demonstrated that TUG1 influenced BTB permeability via binding to miR-144. Furthermore, Knockdown of TUG1 also down-regulated Heat shock transcription factor 2 (HSF2), a transcription factor of the heat shock transcription factor family, which was defined as a direct and functional downstream target of miR-144. HSF2 up-regulated the promoter activities and interacted with the promoters of ZO-1, occludin, and claudin-5 in GECs. In conclusion, our results indicate that knockdown of TUG1 increased BTB permeability via binding to miR-144 and then reducing EC tight junction protein expression by targeting HSF2. Thus, TUG1 may represent a useful future therapeutic target for enhancing BTB permeability.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>26078353</pmid><doi>10.18632/oncotarget.4331</doi><tpages>21</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 3' Untranslated Regions Animals Binding Sites Blood-Brain Barrier - metabolism Blood-Brain Barrier - pathology Brain Neoplasms - genetics Brain Neoplasms - metabolism Brain Neoplasms - pathology Capillary Permeability Cell Line Claudin-5 - genetics Claudin-5 - metabolism Coculture Techniques Electric Impedance Gene Expression Regulation, Neoplastic Glioma - genetics Glioma - metabolism Glioma - pathology Heat-Shock Proteins - genetics Heat-Shock Proteins - metabolism Humans Male Mice, Inbred BALB C Mice, Nude MicroRNAs - genetics MicroRNAs - metabolism Occludin - genetics Occludin - metabolism Research Paper RNA Interference RNA, Long Noncoding - genetics RNA, Long Noncoding - metabolism Tight Junctions - metabolism Transcription Factors - genetics Transcription Factors - metabolism Transcription, Genetic Transfection Tumor Cells, Cultured Zonula Occludens-1 Protein - genetics Zonula Occludens-1 Protein - metabolism |
| title | The long noncoding RNA TUG1 regulates blood-tumor barrier permeability by targeting miR-144 |
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