circ-Sirt1 controls NF-κB activation via sequence-specific interaction and enhancement of SIRT1 expression by binding to miR-132/212 in vascular smooth muscle cells
Abstract NF-κB-mediated inflammatory phenotypic switching of vascular smooth muscle cells (VSMCs) plays a central role in atherosclerosis and neointimal formation. However, little is known about the roles of circRNAs in the regulation of NF-κB signaling. Here, we identify the involvement of circ-Sir...
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| Veröffentlicht in: | Nucleic acids research 2019-04, Vol.47 (7), p.3580-3593 |
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| creator | Kong, Peng Yu, Yuan Wang, Lu Dou, Yong-Qing Zhang, Xu-Hui Cui, Yan Wang, Hai-Yue Yong, Yu-Tao Liu, Ya-Bin Hu, Hai-Juan Cui, Wei Sun, Shao-Guang Li, Bing-Hui Zhang, Fan Han, Mei |
| description | Abstract
NF-κB-mediated inflammatory phenotypic switching of vascular smooth muscle cells (VSMCs) plays a central role in atherosclerosis and neointimal formation. However, little is known about the roles of circRNAs in the regulation of NF-κB signaling. Here, we identify the involvement of circ-Sirt1 that was one of transcripts of SIRT1 host gene in VSMC inflammatory response and neointimal hyperplasia. First, in the cytoplasm, circ-Sirt1 directly interacts with and sequesters NF-κB p65 from nuclear translocation induced by TNF-α in a sequence-dependent manner. The inhibitory complex of circ-Sirt1-NF-κB p65 is not dependent on IκBα. Second, circ-Sirt1 binds to miR-132/212 that interferes with SIRT1 mRNA, and facilitates the expression of host gene SIRT1. Increased SIRT1 results in deacetylation and inactivation of the nuclear NF-κB p65. These findings illustrate that circ-Sirt1 is a novel non-coding RNA regulator of VSMC phenotype. |
| doi_str_mv | 10.1093/nar/gkz141 |
| format | Article |
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NF-κB-mediated inflammatory phenotypic switching of vascular smooth muscle cells (VSMCs) plays a central role in atherosclerosis and neointimal formation. However, little is known about the roles of circRNAs in the regulation of NF-κB signaling. Here, we identify the involvement of circ-Sirt1 that was one of transcripts of SIRT1 host gene in VSMC inflammatory response and neointimal hyperplasia. First, in the cytoplasm, circ-Sirt1 directly interacts with and sequesters NF-κB p65 from nuclear translocation induced by TNF-α in a sequence-dependent manner. The inhibitory complex of circ-Sirt1-NF-κB p65 is not dependent on IκBα. Second, circ-Sirt1 binds to miR-132/212 that interferes with SIRT1 mRNA, and facilitates the expression of host gene SIRT1. Increased SIRT1 results in deacetylation and inactivation of the nuclear NF-κB p65. These findings illustrate that circ-Sirt1 is a novel non-coding RNA regulator of VSMC phenotype.</description><identifier>ISSN: 0305-1048</identifier><identifier>EISSN: 1362-4962</identifier><identifier>DOI: 10.1093/nar/gkz141</identifier><identifier>PMID: 30820544</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Animals ; Carotid Artery Injuries - genetics ; Carotid Artery Injuries - pathology ; Cell Proliferation - genetics ; Cytoplasm - genetics ; Gene Expression Regulation - genetics ; Humans ; Inflammation - genetics ; Inflammation - pathology ; Mice ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Molecular Biology ; Muscle, Smooth, Vascular - metabolism ; Muscle, Smooth, Vascular - pathology ; NF-kappa B - genetics ; NF-KappaB Inhibitor alpha - genetics ; Rats ; RNA-Binding Proteins ; Signal Transduction ; Sirtuin 1 - genetics ; Transcription Factor RelA - genetics ; Tumor Necrosis Factor-alpha - genetics</subject><ispartof>Nucleic acids research, 2019-04, Vol.47 (7), p.3580-3593</ispartof><rights>The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. 2019</rights><rights>The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2531-4fa1b96ffaf6c884e56fc01ad8d236c0d5f166ff497fc68cc7961b9109584cef3</citedby><cites>FETCH-LOGICAL-c2531-4fa1b96ffaf6c884e56fc01ad8d236c0d5f166ff497fc68cc7961b9109584cef3</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/PMC6468289/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468289/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,1604,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30820544$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kong, Peng</creatorcontrib><creatorcontrib>Yu, Yuan</creatorcontrib><creatorcontrib>Wang, Lu</creatorcontrib><creatorcontrib>Dou, Yong-Qing</creatorcontrib><creatorcontrib>Zhang, Xu-Hui</creatorcontrib><creatorcontrib>Cui, Yan</creatorcontrib><creatorcontrib>Wang, Hai-Yue</creatorcontrib><creatorcontrib>Yong, Yu-Tao</creatorcontrib><creatorcontrib>Liu, Ya-Bin</creatorcontrib><creatorcontrib>Hu, Hai-Juan</creatorcontrib><creatorcontrib>Cui, Wei</creatorcontrib><creatorcontrib>Sun, Shao-Guang</creatorcontrib><creatorcontrib>Li, Bing-Hui</creatorcontrib><creatorcontrib>Zhang, Fan</creatorcontrib><creatorcontrib>Han, Mei</creatorcontrib><title>circ-Sirt1 controls NF-κB activation via sequence-specific interaction and enhancement of SIRT1 expression by binding to miR-132/212 in vascular smooth muscle cells</title><title>Nucleic acids research</title><addtitle>Nucleic Acids Res</addtitle><description>Abstract
NF-κB-mediated inflammatory phenotypic switching of vascular smooth muscle cells (VSMCs) plays a central role in atherosclerosis and neointimal formation. However, little is known about the roles of circRNAs in the regulation of NF-κB signaling. Here, we identify the involvement of circ-Sirt1 that was one of transcripts of SIRT1 host gene in VSMC inflammatory response and neointimal hyperplasia. First, in the cytoplasm, circ-Sirt1 directly interacts with and sequesters NF-κB p65 from nuclear translocation induced by TNF-α in a sequence-dependent manner. The inhibitory complex of circ-Sirt1-NF-κB p65 is not dependent on IκBα. Second, circ-Sirt1 binds to miR-132/212 that interferes with SIRT1 mRNA, and facilitates the expression of host gene SIRT1. Increased SIRT1 results in deacetylation and inactivation of the nuclear NF-κB p65. These findings illustrate that circ-Sirt1 is a novel non-coding RNA regulator of VSMC phenotype.</description><subject>Animals</subject><subject>Carotid Artery Injuries - genetics</subject><subject>Carotid Artery Injuries - pathology</subject><subject>Cell Proliferation - genetics</subject><subject>Cytoplasm - genetics</subject><subject>Gene Expression Regulation - genetics</subject><subject>Humans</subject><subject>Inflammation - genetics</subject><subject>Inflammation - pathology</subject><subject>Mice</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Molecular Biology</subject><subject>Muscle, Smooth, Vascular - metabolism</subject><subject>Muscle, Smooth, Vascular - pathology</subject><subject>NF-kappa B - genetics</subject><subject>NF-KappaB Inhibitor alpha - genetics</subject><subject>Rats</subject><subject>RNA-Binding Proteins</subject><subject>Signal Transduction</subject><subject>Sirtuin 1 - genetics</subject><subject>Transcription Factor RelA - genetics</subject><subject>Tumor Necrosis Factor-alpha - genetics</subject><issn>0305-1048</issn><issn>1362-4962</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><sourceid>EIF</sourceid><recordid>eNp9kcFu1DAQhi1ERZfChQdAviAhpHRtx3GcCxJUlFaqQGrL2fJO7F1DYqe2s6K8Dy_BQ_BM9WpLBRdOPsw333jmR-gFJceUdPXS67hcf_tBOX2EFrQWrOKdYI_RgtSkqSjh8hA9TekrIQVp-BN0WBPJSMP5Av0EF6G6cjFTDMHnGIaEP51Wv3-9xxqy2-rsgsdbp3EyN7PxYKo0GXDWAXY-m7ijCqF9j43f6AKMxmccLL46v7ym2Hyfoklpx6xu8cr53vk1zgGP7rKiNVsyyooJb3WCedARpzGEvMHjnGAwGMwwpGfowOohmef37xH6cvrh-uSsuvj88fzk3UUFrKlpxa2mq05Yq60AKblphAVCdS97VgsgfWOpKGXetRaEBGg7URrKERvJwdj6CL3de6d5NZoeyiJRD2qKbtTxVgXt1L8V7zZqHbZKcCGZ7Irg9b0ghnKtlNXo0m4F7U2Yk2JUtg0jbdsU9M0ehRhSisY-jKFE7XJVJVe1z7XAL__-2AP6J8gCvNoDYZ7-J7oD6LWvzw</recordid><startdate>20190423</startdate><enddate>20190423</enddate><creator>Kong, Peng</creator><creator>Yu, Yuan</creator><creator>Wang, Lu</creator><creator>Dou, Yong-Qing</creator><creator>Zhang, Xu-Hui</creator><creator>Cui, Yan</creator><creator>Wang, Hai-Yue</creator><creator>Yong, Yu-Tao</creator><creator>Liu, Ya-Bin</creator><creator>Hu, Hai-Juan</creator><creator>Cui, Wei</creator><creator>Sun, Shao-Guang</creator><creator>Li, Bing-Hui</creator><creator>Zhang, Fan</creator><creator>Han, Mei</creator><general>Oxford University Press</general><scope>TOX</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></search><sort><creationdate>20190423</creationdate><title>circ-Sirt1 controls NF-κB activation via sequence-specific interaction and enhancement of SIRT1 expression by binding to miR-132/212 in vascular smooth muscle cells</title><author>Kong, Peng ; Yu, Yuan ; Wang, Lu ; Dou, Yong-Qing ; Zhang, Xu-Hui ; Cui, Yan ; Wang, Hai-Yue ; Yong, Yu-Tao ; Liu, Ya-Bin ; Hu, Hai-Juan ; Cui, Wei ; Sun, Shao-Guang ; Li, Bing-Hui ; Zhang, Fan ; Han, Mei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2531-4fa1b96ffaf6c884e56fc01ad8d236c0d5f166ff497fc68cc7961b9109584cef3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Carotid Artery Injuries - genetics</topic><topic>Carotid Artery Injuries - pathology</topic><topic>Cell Proliferation - genetics</topic><topic>Cytoplasm - genetics</topic><topic>Gene Expression Regulation - genetics</topic><topic>Humans</topic><topic>Inflammation - genetics</topic><topic>Inflammation - pathology</topic><topic>Mice</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Molecular Biology</topic><topic>Muscle, Smooth, Vascular - metabolism</topic><topic>Muscle, Smooth, Vascular - pathology</topic><topic>NF-kappa B - genetics</topic><topic>NF-KappaB Inhibitor alpha - genetics</topic><topic>Rats</topic><topic>RNA-Binding Proteins</topic><topic>Signal Transduction</topic><topic>Sirtuin 1 - genetics</topic><topic>Transcription Factor RelA - genetics</topic><topic>Tumor Necrosis Factor-alpha - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kong, Peng</creatorcontrib><creatorcontrib>Yu, Yuan</creatorcontrib><creatorcontrib>Wang, Lu</creatorcontrib><creatorcontrib>Dou, Yong-Qing</creatorcontrib><creatorcontrib>Zhang, Xu-Hui</creatorcontrib><creatorcontrib>Cui, Yan</creatorcontrib><creatorcontrib>Wang, Hai-Yue</creatorcontrib><creatorcontrib>Yong, Yu-Tao</creatorcontrib><creatorcontrib>Liu, Ya-Bin</creatorcontrib><creatorcontrib>Hu, Hai-Juan</creatorcontrib><creatorcontrib>Cui, Wei</creatorcontrib><creatorcontrib>Sun, Shao-Guang</creatorcontrib><creatorcontrib>Li, Bing-Hui</creatorcontrib><creatorcontrib>Zhang, Fan</creatorcontrib><creatorcontrib>Han, Mei</creatorcontrib><collection>Access via Oxford University Press (Open Access Collection)</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><jtitle>Nucleic acids research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kong, Peng</au><au>Yu, Yuan</au><au>Wang, Lu</au><au>Dou, Yong-Qing</au><au>Zhang, Xu-Hui</au><au>Cui, Yan</au><au>Wang, Hai-Yue</au><au>Yong, Yu-Tao</au><au>Liu, Ya-Bin</au><au>Hu, Hai-Juan</au><au>Cui, Wei</au><au>Sun, Shao-Guang</au><au>Li, Bing-Hui</au><au>Zhang, Fan</au><au>Han, Mei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>circ-Sirt1 controls NF-κB activation via sequence-specific interaction and enhancement of SIRT1 expression by binding to miR-132/212 in vascular smooth muscle cells</atitle><jtitle>Nucleic acids research</jtitle><addtitle>Nucleic Acids Res</addtitle><date>2019-04-23</date><risdate>2019</risdate><volume>47</volume><issue>7</issue><spage>3580</spage><epage>3593</epage><pages>3580-3593</pages><issn>0305-1048</issn><eissn>1362-4962</eissn><abstract>Abstract
NF-κB-mediated inflammatory phenotypic switching of vascular smooth muscle cells (VSMCs) plays a central role in atherosclerosis and neointimal formation. However, little is known about the roles of circRNAs in the regulation of NF-κB signaling. Here, we identify the involvement of circ-Sirt1 that was one of transcripts of SIRT1 host gene in VSMC inflammatory response and neointimal hyperplasia. First, in the cytoplasm, circ-Sirt1 directly interacts with and sequesters NF-κB p65 from nuclear translocation induced by TNF-α in a sequence-dependent manner. The inhibitory complex of circ-Sirt1-NF-κB p65 is not dependent on IκBα. Second, circ-Sirt1 binds to miR-132/212 that interferes with SIRT1 mRNA, and facilitates the expression of host gene SIRT1. Increased SIRT1 results in deacetylation and inactivation of the nuclear NF-κB p65. These findings illustrate that circ-Sirt1 is a novel non-coding RNA regulator of VSMC phenotype.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>30820544</pmid><doi>10.1093/nar/gkz141</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Carotid Artery Injuries - genetics Carotid Artery Injuries - pathology Cell Proliferation - genetics Cytoplasm - genetics Gene Expression Regulation - genetics Humans Inflammation - genetics Inflammation - pathology Mice MicroRNAs - genetics MicroRNAs - metabolism Molecular Biology Muscle, Smooth, Vascular - metabolism Muscle, Smooth, Vascular - pathology NF-kappa B - genetics NF-KappaB Inhibitor alpha - genetics Rats RNA-Binding Proteins Signal Transduction Sirtuin 1 - genetics Transcription Factor RelA - genetics Tumor Necrosis Factor-alpha - genetics |
| title | circ-Sirt1 controls NF-κB activation via sequence-specific interaction and enhancement of SIRT1 expression by binding to miR-132/212 in vascular smooth muscle cells |
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