SIRT1 suppresses colorectal cancer metastasis by transcriptional repression of miR-15b-5p
The class III deacetylase sirtuin 1 (SIRT1), a member of the sirtuin family proteins, plays a key role in many types of cancers including colorectal cancer (CRC). Here we report that SIRT1 suppressed CRC metastasis in vitro and in vivo as a negative regulator for miR-15b-5p transcription. Mechanisti...
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| Veröffentlicht in: | Cancer letters 2017-11, Vol.409, p.104-115 |
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| container_title | Cancer letters |
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| creator | Sun, Li-Na Zhi, Zheng Chen, Liang-Yan Zhou, Qun Li, Xiu-Ming Gan, Wen-Juan Chen, Shu Yang, Meng Liu, Yao Shen, Tong Xu, Yong Li, Jian-Ming |
| description | The class III deacetylase sirtuin 1 (SIRT1), a member of the sirtuin family proteins, plays a key role in many types of cancers including colorectal cancer (CRC). Here we report that SIRT1 suppressed CRC metastasis in vitro and in vivo as a negative regulator for miR-15b-5p transcription. Mechanistically, SIRT1 impaired regulatory effects of activator protein (AP-1) on miR-15b-5p trans-activation through deacetylation of AP-1. Importantly, acyl-CoA oxidase 1 (ACOX1), a key enzyme of the fatty acid oxidation (FAO) pathway, was found as a direct target for miR-15b-5p. SIRT1 expression was positively correlated with ACOX1 expression in CRC cells and in xenografts. Moreover, ACOX1 overexpression attenuated the augmentation of migration and invasion of CRC cells by miR-15b-5p overexpression. In conclusion, our study demonstrated a functional role of the SIRT1/miR-15b-5p/ACOX1 axis in CRC metastasis and suggested a potential target for metastatic CRC therapy.
•SIRT1 is a tumor suppressor gene in colorectal cancer patients.•SIRT1 suppresses CRC metastasis by blocking miR-15b-5p transcription.•SIRT1 suppresses miR-15b-5p transcription by impairing the binding of AP-1 to its promoter.•SIRT1 inhibits CRC metastasis through SIRT1/miR-15b-5p/ACOX1 axis. |
| doi_str_mv | 10.1016/j.canlet.2017.09.001 |
| format | Article |
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•SIRT1 is a tumor suppressor gene in colorectal cancer patients.•SIRT1 suppresses CRC metastasis by blocking miR-15b-5p transcription.•SIRT1 suppresses miR-15b-5p transcription by impairing the binding of AP-1 to its promoter.•SIRT1 inhibits CRC metastasis through SIRT1/miR-15b-5p/ACOX1 axis.</description><identifier>ISSN: 0304-3835</identifier><identifier>EISSN: 1872-7980</identifier><identifier>DOI: 10.1016/j.canlet.2017.09.001</identifier><identifier>PMID: 28923398</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>3-Hydroxyacyl CoA Dehydrogenases - metabolism ; Acetyl-CoA C-Acyltransferase - metabolism ; Activator protein 1 ; Acyl-CoA oxidase ; Animals ; Apoptosis ; Breast cancer ; Caco-2 Cells ; Cancer metastasis ; Carbon-Carbon Double Bond Isomerases - metabolism ; Cell Line, Tumor ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - metabolism ; Colorectal Neoplasms - pathology ; Deacetylation ; Enoyl-CoA Hydratase - metabolism ; Experiments ; Fatty-acid oxidation ; Gene silencing ; HCT116 Cells ; Heterografts ; HT29 Cells ; Humans ; Lung cancer ; Metabolism ; Metastases ; Metastasis ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; microRNA ; MicroRNAs ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Neoplasm Metastasis ; Oxidation ; Proteins ; Racemases and Epimerases - metabolism ; Rodents ; Signal Transduction ; SIRT1 ; SIRT1 protein ; Sirtuin 1 - genetics ; Sirtuin 1 - metabolism ; Transcription factors ; Transcription, Genetic ; Transfection ; Tumors ; Xenografts</subject><ispartof>Cancer letters, 2017-11, Vol.409, p.104-115</ispartof><rights>2017 Elsevier B.V.</rights><rights>Copyright © 2017 Elsevier B.V. All rights reserved.</rights><rights>2017. Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-4e65b6d85f8a0d8db00d4fe477a77c06b3e99afa5d793cc85eae4144e0755ddf3</citedby><cites>FETCH-LOGICAL-c390t-4e65b6d85f8a0d8db00d4fe477a77c06b3e99afa5d793cc85eae4144e0755ddf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.canlet.2017.09.001$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28923398$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sun, Li-Na</creatorcontrib><creatorcontrib>Zhi, Zheng</creatorcontrib><creatorcontrib>Chen, Liang-Yan</creatorcontrib><creatorcontrib>Zhou, Qun</creatorcontrib><creatorcontrib>Li, Xiu-Ming</creatorcontrib><creatorcontrib>Gan, Wen-Juan</creatorcontrib><creatorcontrib>Chen, Shu</creatorcontrib><creatorcontrib>Yang, Meng</creatorcontrib><creatorcontrib>Liu, Yao</creatorcontrib><creatorcontrib>Shen, Tong</creatorcontrib><creatorcontrib>Xu, Yong</creatorcontrib><creatorcontrib>Li, Jian-Ming</creatorcontrib><title>SIRT1 suppresses colorectal cancer metastasis by transcriptional repression of miR-15b-5p</title><title>Cancer letters</title><addtitle>Cancer Lett</addtitle><description>The class III deacetylase sirtuin 1 (SIRT1), a member of the sirtuin family proteins, plays a key role in many types of cancers including colorectal cancer (CRC). Here we report that SIRT1 suppressed CRC metastasis in vitro and in vivo as a negative regulator for miR-15b-5p transcription. Mechanistically, SIRT1 impaired regulatory effects of activator protein (AP-1) on miR-15b-5p trans-activation through deacetylation of AP-1. Importantly, acyl-CoA oxidase 1 (ACOX1), a key enzyme of the fatty acid oxidation (FAO) pathway, was found as a direct target for miR-15b-5p. SIRT1 expression was positively correlated with ACOX1 expression in CRC cells and in xenografts. Moreover, ACOX1 overexpression attenuated the augmentation of migration and invasion of CRC cells by miR-15b-5p overexpression. In conclusion, our study demonstrated a functional role of the SIRT1/miR-15b-5p/ACOX1 axis in CRC metastasis and suggested a potential target for metastatic CRC therapy.
•SIRT1 is a tumor suppressor gene in colorectal cancer patients.•SIRT1 suppresses CRC metastasis by blocking miR-15b-5p transcription.•SIRT1 suppresses miR-15b-5p transcription by impairing the binding of AP-1 to its promoter.•SIRT1 inhibits CRC metastasis through SIRT1/miR-15b-5p/ACOX1 axis.</description><subject>3-Hydroxyacyl CoA Dehydrogenases - metabolism</subject><subject>Acetyl-CoA C-Acyltransferase - metabolism</subject><subject>Activator protein 1</subject><subject>Acyl-CoA oxidase</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Breast cancer</subject><subject>Caco-2 Cells</subject><subject>Cancer metastasis</subject><subject>Carbon-Carbon Double Bond Isomerases - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Deacetylation</subject><subject>Enoyl-CoA Hydratase - metabolism</subject><subject>Experiments</subject><subject>Fatty-acid oxidation</subject><subject>Gene silencing</subject><subject>HCT116 Cells</subject><subject>Heterografts</subject><subject>HT29 Cells</subject><subject>Humans</subject><subject>Lung cancer</subject><subject>Metabolism</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>microRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Neoplasm Metastasis</subject><subject>Oxidation</subject><subject>Proteins</subject><subject>Racemases and Epimerases - metabolism</subject><subject>Rodents</subject><subject>Signal Transduction</subject><subject>SIRT1</subject><subject>SIRT1 protein</subject><subject>Sirtuin 1 - genetics</subject><subject>Sirtuin 1 - metabolism</subject><subject>Transcription factors</subject><subject>Transcription, Genetic</subject><subject>Transfection</subject><subject>Tumors</subject><subject>Xenografts</subject><issn>0304-3835</issn><issn>1872-7980</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1r3DAQhkVpaTZJ_0Ephl5ysTuyJEu6FErIFwQKaXrIScjSGLTYK1eyA_n31WbTHnIIDAwDzzvDPIR8ptBQoN23bePsbsSlaYHKBnQDQN-RDVWyraVW8J5sgAGvmWLiiBznvAUAwaX4SI5apVvGtNqQh183d_e0yus8J8wZc-XiGBO6xY5VOeAwVRMuNpcKueqfqiXZXXYpzEuIuwIlfE6WoYpDNYW7moq-FvMp-TDYMeOnl35Cfl9e3J9f17c_r27Of9zWjmlYao6d6DuvxKAseOV7AM8H5FJaKR10PUOt7WCFl5o5pwRa5JRzBCmE9wM7IWeHvXOKf1bMi5lCdjiOdodxzYZqDkJLTUVBv75Ct3FN5YlnSneCSdoWih8ol2LOCQczpzDZ9GQomL16szUH9Wav3oA2RX2JfXlZvvYT-v-hf64L8P0AYLHxGDCZ7AIWwz7sfRsfw9sX_gLFU5bh</recordid><startdate>20171128</startdate><enddate>20171128</enddate><creator>Sun, Li-Na</creator><creator>Zhi, Zheng</creator><creator>Chen, Liang-Yan</creator><creator>Zhou, Qun</creator><creator>Li, Xiu-Ming</creator><creator>Gan, Wen-Juan</creator><creator>Chen, Shu</creator><creator>Yang, Meng</creator><creator>Liu, Yao</creator><creator>Shen, Tong</creator><creator>Xu, Yong</creator><creator>Li, Jian-Ming</creator><general>Elsevier B.V</general><general>Elsevier Limited</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>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>20171128</creationdate><title>SIRT1 suppresses colorectal cancer metastasis by transcriptional repression of miR-15b-5p</title><author>Sun, Li-Na ; Zhi, Zheng ; Chen, Liang-Yan ; Zhou, Qun ; Li, Xiu-Ming ; Gan, Wen-Juan ; Chen, Shu ; Yang, Meng ; Liu, Yao ; Shen, Tong ; Xu, Yong ; Li, Jian-Ming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-4e65b6d85f8a0d8db00d4fe477a77c06b3e99afa5d793cc85eae4144e0755ddf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>3-Hydroxyacyl CoA Dehydrogenases - metabolism</topic><topic>Acetyl-CoA C-Acyltransferase - metabolism</topic><topic>Activator protein 1</topic><topic>Acyl-CoA oxidase</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Breast cancer</topic><topic>Caco-2 Cells</topic><topic>Cancer metastasis</topic><topic>Carbon-Carbon Double Bond Isomerases - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - metabolism</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Deacetylation</topic><topic>Enoyl-CoA Hydratase - metabolism</topic><topic>Experiments</topic><topic>Fatty-acid oxidation</topic><topic>Gene silencing</topic><topic>HCT116 Cells</topic><topic>Heterografts</topic><topic>HT29 Cells</topic><topic>Humans</topic><topic>Lung cancer</topic><topic>Metabolism</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>microRNA</topic><topic>MicroRNAs</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Neoplasm Metastasis</topic><topic>Oxidation</topic><topic>Proteins</topic><topic>Racemases and Epimerases - metabolism</topic><topic>Rodents</topic><topic>Signal Transduction</topic><topic>SIRT1</topic><topic>SIRT1 protein</topic><topic>Sirtuin 1 - genetics</topic><topic>Sirtuin 1 - metabolism</topic><topic>Transcription factors</topic><topic>Transcription, Genetic</topic><topic>Transfection</topic><topic>Tumors</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sun, Li-Na</creatorcontrib><creatorcontrib>Zhi, Zheng</creatorcontrib><creatorcontrib>Chen, Liang-Yan</creatorcontrib><creatorcontrib>Zhou, Qun</creatorcontrib><creatorcontrib>Li, Xiu-Ming</creatorcontrib><creatorcontrib>Gan, Wen-Juan</creatorcontrib><creatorcontrib>Chen, Shu</creatorcontrib><creatorcontrib>Yang, Meng</creatorcontrib><creatorcontrib>Liu, Yao</creatorcontrib><creatorcontrib>Shen, Tong</creatorcontrib><creatorcontrib>Xu, Yong</creatorcontrib><creatorcontrib>Li, Jian-Ming</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sun, Li-Na</au><au>Zhi, Zheng</au><au>Chen, Liang-Yan</au><au>Zhou, Qun</au><au>Li, Xiu-Ming</au><au>Gan, Wen-Juan</au><au>Chen, Shu</au><au>Yang, Meng</au><au>Liu, Yao</au><au>Shen, Tong</au><au>Xu, Yong</au><au>Li, Jian-Ming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SIRT1 suppresses colorectal cancer metastasis by transcriptional repression of miR-15b-5p</atitle><jtitle>Cancer letters</jtitle><addtitle>Cancer Lett</addtitle><date>2017-11-28</date><risdate>2017</risdate><volume>409</volume><spage>104</spage><epage>115</epage><pages>104-115</pages><issn>0304-3835</issn><eissn>1872-7980</eissn><abstract>The class III deacetylase sirtuin 1 (SIRT1), a member of the sirtuin family proteins, plays a key role in many types of cancers including colorectal cancer (CRC). Here we report that SIRT1 suppressed CRC metastasis in vitro and in vivo as a negative regulator for miR-15b-5p transcription. Mechanistically, SIRT1 impaired regulatory effects of activator protein (AP-1) on miR-15b-5p trans-activation through deacetylation of AP-1. Importantly, acyl-CoA oxidase 1 (ACOX1), a key enzyme of the fatty acid oxidation (FAO) pathway, was found as a direct target for miR-15b-5p. SIRT1 expression was positively correlated with ACOX1 expression in CRC cells and in xenografts. Moreover, ACOX1 overexpression attenuated the augmentation of migration and invasion of CRC cells by miR-15b-5p overexpression. In conclusion, our study demonstrated a functional role of the SIRT1/miR-15b-5p/ACOX1 axis in CRC metastasis and suggested a potential target for metastatic CRC therapy.
•SIRT1 is a tumor suppressor gene in colorectal cancer patients.•SIRT1 suppresses CRC metastasis by blocking miR-15b-5p transcription.•SIRT1 suppresses miR-15b-5p transcription by impairing the binding of AP-1 to its promoter.•SIRT1 inhibits CRC metastasis through SIRT1/miR-15b-5p/ACOX1 axis.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>28923398</pmid><doi>10.1016/j.canlet.2017.09.001</doi><tpages>12</tpages></addata></record> |
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| subjects | 3-Hydroxyacyl CoA Dehydrogenases - metabolism Acetyl-CoA C-Acyltransferase - metabolism Activator protein 1 Acyl-CoA oxidase Animals Apoptosis Breast cancer Caco-2 Cells Cancer metastasis Carbon-Carbon Double Bond Isomerases - metabolism Cell Line, Tumor Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - genetics Colorectal Neoplasms - metabolism Colorectal Neoplasms - pathology Deacetylation Enoyl-CoA Hydratase - metabolism Experiments Fatty-acid oxidation Gene silencing HCT116 Cells Heterografts HT29 Cells Humans Lung cancer Metabolism Metastases Metastasis Mice Mice, Inbred BALB C Mice, Nude microRNA MicroRNAs MicroRNAs - genetics MicroRNAs - metabolism Neoplasm Metastasis Oxidation Proteins Racemases and Epimerases - metabolism Rodents Signal Transduction SIRT1 SIRT1 protein Sirtuin 1 - genetics Sirtuin 1 - metabolism Transcription factors Transcription, Genetic Transfection Tumors Xenografts |
| title | SIRT1 suppresses colorectal cancer metastasis by transcriptional repression of miR-15b-5p |
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