miR-124 inhibits cell proliferation, migration and invasion by directly targeting SOX9 in lung adenocarcinoma
Accumulating evidence indicates that dysregulation of microRNAs (miRNAs) may contribute to the initiation and progression of cancer. However, the role of miR-124 in lung adenocarcinoma (ADC) and the underlying mechanisms through which miR-124 exerts its functions are not completely understood. In th...
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Veröffentlicht in: | Oncology reports 2016-05, Vol.35 (5), p.3115-3121 |
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description | Accumulating evidence indicates that dysregulation of microRNAs (miRNAs) may contribute to the initiation and progression of cancer. However, the role of miR-124 in lung adenocarcinoma (ADC) and the underlying mechanisms through which miR-124 exerts its functions are not completely understood. In the present study, we detected miR-124 and SOX9 expression in lung ADC tissues. The results showed that miR-124 was significantly downregulated in the lung ADC tissues compared with that noted in the corresponding non-cancerous lung tissues and the level of SOX9 protein was inversely associated with the expression of miR-124. The study in human lung ADC cell line A549 demonstrated that upregulation of miR-124 could inhibit cell proliferation, migration and invasion. The bioinformatic analysis showed that there was a putative miR-124 binding site in the 3′ untranslated region (3′UTR) of SOX9. Using a luciferase reporter assay, we verified that SOX9 is a direct target of miR-124. Furthermore, overexpression of miR-124 repressed SOX9 expression, whereas inhibition of miR-124 increased expression of SOX9 in the A549 cells. Finally, we identified that SOX9 was a functional mediator of miR-124 in A549 cells. Taken together, our results suggest that miR-124 functions as a tumor suppressor in lung ADC by directly targeting SOX9 and it may be a promising candidate for miR-based therapy against lung ADC. |
doi_str_mv | 10.3892/or.2016.4648 |
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However, the role of miR-124 in lung adenocarcinoma (ADC) and the underlying mechanisms through which miR-124 exerts its functions are not completely understood. In the present study, we detected miR-124 and SOX9 expression in lung ADC tissues. The results showed that miR-124 was significantly downregulated in the lung ADC tissues compared with that noted in the corresponding non-cancerous lung tissues and the level of SOX9 protein was inversely associated with the expression of miR-124. The study in human lung ADC cell line A549 demonstrated that upregulation of miR-124 could inhibit cell proliferation, migration and invasion. The bioinformatic analysis showed that there was a putative miR-124 binding site in the 3′ untranslated region (3′UTR) of SOX9. Using a luciferase reporter assay, we verified that SOX9 is a direct target of miR-124. Furthermore, overexpression of miR-124 repressed SOX9 expression, whereas inhibition of miR-124 increased expression of SOX9 in the A549 cells. Finally, we identified that SOX9 was a functional mediator of miR-124 in A549 cells. Taken together, our results suggest that miR-124 functions as a tumor suppressor in lung ADC by directly targeting SOX9 and it may be a promising candidate for miR-based therapy against lung ADC.</description><identifier>ISSN: 1021-335X</identifier><identifier>EISSN: 1791-2431</identifier><identifier>DOI: 10.3892/or.2016.4648</identifier><identifier>PMID: 26935152</identifier><language>eng</language><publisher>Greece: D.A. Spandidos</publisher><subject>A549 Cells ; Adenocarcinoma ; Adenocarcinoma of Lung ; Base Sequence ; Cell growth ; Cell Movement ; Cell Proliferation ; Development and progression ; Down-Regulation ; Gene expression ; Gene Expression Regulation, Neoplastic ; Genes ; Genetic aspects ; Health aspects ; Humans ; invasion ; lung adenocarcinoma ; Lung cancer ; Lung Neoplasms ; MicroRNA ; MicroRNAs - physiology ; migration ; miR-124 ; Neoplasm Invasiveness ; Ovarian cancer ; proliferation ; Properties ; Prostate ; RNA Interference ; SOX9 ; SOX9 Transcription Factor - genetics ; SOX9 Transcription Factor - metabolism ; Studies ; Superoxide dismutase</subject><ispartof>Oncology reports, 2016-05, Vol.35 (5), p.3115-3121</ispartof><rights>Copyright © 2016, Spandidos Publications</rights><rights>COPYRIGHT 2016 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c486t-6a958aaec1466af97df176423f1b23008a870f7e21980ac794c786485197d84f3</citedby><cites>FETCH-LOGICAL-c486t-6a958aaec1466af97df176423f1b23008a870f7e21980ac794c786485197d84f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26935152$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>WANG, XIAOYING</creatorcontrib><creatorcontrib>LIU, YANLI</creatorcontrib><creatorcontrib>LIU, XIAOLI</creatorcontrib><creatorcontrib>YANG, JINGYAN</creatorcontrib><creatorcontrib>TENG, GUOXIN</creatorcontrib><creatorcontrib>ZHANG, LULU</creatorcontrib><creatorcontrib>ZHOU, CHENGJUN</creatorcontrib><title>miR-124 inhibits cell proliferation, migration and invasion by directly targeting SOX9 in lung adenocarcinoma</title><title>Oncology reports</title><addtitle>Oncol Rep</addtitle><description>Accumulating evidence indicates that dysregulation of microRNAs (miRNAs) may contribute to the initiation and progression of cancer. However, the role of miR-124 in lung adenocarcinoma (ADC) and the underlying mechanisms through which miR-124 exerts its functions are not completely understood. In the present study, we detected miR-124 and SOX9 expression in lung ADC tissues. The results showed that miR-124 was significantly downregulated in the lung ADC tissues compared with that noted in the corresponding non-cancerous lung tissues and the level of SOX9 protein was inversely associated with the expression of miR-124. The study in human lung ADC cell line A549 demonstrated that upregulation of miR-124 could inhibit cell proliferation, migration and invasion. The bioinformatic analysis showed that there was a putative miR-124 binding site in the 3′ untranslated region (3′UTR) of SOX9. Using a luciferase reporter assay, we verified that SOX9 is a direct target of miR-124. Furthermore, overexpression of miR-124 repressed SOX9 expression, whereas inhibition of miR-124 increased expression of SOX9 in the A549 cells. Finally, we identified that SOX9 was a functional mediator of miR-124 in A549 cells. Taken together, our results suggest that miR-124 functions as a tumor suppressor in lung ADC by directly targeting SOX9 and it may be a promising candidate for miR-based therapy against lung ADC.</description><subject>A549 Cells</subject><subject>Adenocarcinoma</subject><subject>Adenocarcinoma of Lung</subject><subject>Base Sequence</subject><subject>Cell growth</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Development and progression</subject><subject>Down-Regulation</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Humans</subject><subject>invasion</subject><subject>lung adenocarcinoma</subject><subject>Lung cancer</subject><subject>Lung Neoplasms</subject><subject>MicroRNA</subject><subject>MicroRNAs - physiology</subject><subject>migration</subject><subject>miR-124</subject><subject>Neoplasm Invasiveness</subject><subject>Ovarian cancer</subject><subject>proliferation</subject><subject>Properties</subject><subject>Prostate</subject><subject>RNA Interference</subject><subject>SOX9</subject><subject>SOX9 Transcription Factor - genetics</subject><subject>SOX9 Transcription Factor - metabolism</subject><subject>Studies</subject><subject>Superoxide dismutase</subject><issn>1021-335X</issn><issn>1791-2431</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNptkl1rFDEUhgdRbK3eeS0DgnjRWXPynctSWhUKBT-gdyGbSXZTZpI1mSnsvzfD1taK5CLnhOec5M15m-YtoBWRCn9KeYUR8BXlVD5rjkEo6DAl8LzGCENHCLs5al6VcosQFoirl80R5oowYPi4GcfwrQNM2xC3YR2m0lo3DO0upyF4l80UUjxtx7A5hK2JfUXvTFmS9b7tQ3Z2GvbtZPLGTSFu2u_XN6oy7TDXxPQuJmuyDTGN5nXzwpuhuDf3-0nz8_Lix_mX7ur689fzs6vOUsmnjhvFpDHOAuXceCV6D4JTTDysMUFIGimQFw6DkshYoagVsspnUFFJPTlpPh76Vh2_ZlcmPYayCDPRpbloEEJJiRmXFX3_D3qb5hzr6zQogrkUFONHamMGp0P0acrGLk31GWUgqcIKKrX6D1VX78ZgU3Q-1PMnBR_-Ktg6M0zbkoZ5-eryFDw9gDanUrLzepfDaPJeA9KLDXTKerGBXmxQ8Xf3oub16PoH-M_cHy8uuzrR0KfywKTcEdYh1hEARn4DSnW2cA</recordid><startdate>20160501</startdate><enddate>20160501</enddate><creator>WANG, XIAOYING</creator><creator>LIU, YANLI</creator><creator>LIU, XIAOLI</creator><creator>YANG, JINGYAN</creator><creator>TENG, GUOXIN</creator><creator>ZHANG, LULU</creator><creator>ZHOU, CHENGJUN</creator><general>D.A. Spandidos</general><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20160501</creationdate><title>miR-124 inhibits cell proliferation, migration and invasion by directly targeting SOX9 in lung adenocarcinoma</title><author>WANG, XIAOYING ; LIU, YANLI ; LIU, XIAOLI ; YANG, JINGYAN ; TENG, GUOXIN ; ZHANG, LULU ; ZHOU, CHENGJUN</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c486t-6a958aaec1466af97df176423f1b23008a870f7e21980ac794c786485197d84f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>A549 Cells</topic><topic>Adenocarcinoma</topic><topic>Adenocarcinoma of Lung</topic><topic>Base Sequence</topic><topic>Cell growth</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Development and progression</topic><topic>Down-Regulation</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Humans</topic><topic>invasion</topic><topic>lung adenocarcinoma</topic><topic>Lung cancer</topic><topic>Lung Neoplasms</topic><topic>MicroRNA</topic><topic>MicroRNAs - physiology</topic><topic>migration</topic><topic>miR-124</topic><topic>Neoplasm Invasiveness</topic><topic>Ovarian cancer</topic><topic>proliferation</topic><topic>Properties</topic><topic>Prostate</topic><topic>RNA Interference</topic><topic>SOX9</topic><topic>SOX9 Transcription Factor - genetics</topic><topic>SOX9 Transcription Factor - metabolism</topic><topic>Studies</topic><topic>Superoxide dismutase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>WANG, XIAOYING</creatorcontrib><creatorcontrib>LIU, YANLI</creatorcontrib><creatorcontrib>LIU, XIAOLI</creatorcontrib><creatorcontrib>YANG, JINGYAN</creatorcontrib><creatorcontrib>TENG, GUOXIN</creatorcontrib><creatorcontrib>ZHANG, LULU</creatorcontrib><creatorcontrib>ZHOU, CHENGJUN</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Oncology reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>WANG, XIAOYING</au><au>LIU, YANLI</au><au>LIU, XIAOLI</au><au>YANG, JINGYAN</au><au>TENG, GUOXIN</au><au>ZHANG, LULU</au><au>ZHOU, CHENGJUN</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>miR-124 inhibits cell proliferation, migration and invasion by directly targeting SOX9 in lung adenocarcinoma</atitle><jtitle>Oncology reports</jtitle><addtitle>Oncol Rep</addtitle><date>2016-05-01</date><risdate>2016</risdate><volume>35</volume><issue>5</issue><spage>3115</spage><epage>3121</epage><pages>3115-3121</pages><issn>1021-335X</issn><eissn>1791-2431</eissn><abstract>Accumulating evidence indicates that dysregulation of microRNAs (miRNAs) may contribute to the initiation and progression of cancer. However, the role of miR-124 in lung adenocarcinoma (ADC) and the underlying mechanisms through which miR-124 exerts its functions are not completely understood. In the present study, we detected miR-124 and SOX9 expression in lung ADC tissues. The results showed that miR-124 was significantly downregulated in the lung ADC tissues compared with that noted in the corresponding non-cancerous lung tissues and the level of SOX9 protein was inversely associated with the expression of miR-124. The study in human lung ADC cell line A549 demonstrated that upregulation of miR-124 could inhibit cell proliferation, migration and invasion. The bioinformatic analysis showed that there was a putative miR-124 binding site in the 3′ untranslated region (3′UTR) of SOX9. Using a luciferase reporter assay, we verified that SOX9 is a direct target of miR-124. Furthermore, overexpression of miR-124 repressed SOX9 expression, whereas inhibition of miR-124 increased expression of SOX9 in the A549 cells. Finally, we identified that SOX9 was a functional mediator of miR-124 in A549 cells. Taken together, our results suggest that miR-124 functions as a tumor suppressor in lung ADC by directly targeting SOX9 and it may be a promising candidate for miR-based therapy against lung ADC.</abstract><cop>Greece</cop><pub>D.A. Spandidos</pub><pmid>26935152</pmid><doi>10.3892/or.2016.4648</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | A549 Cells Adenocarcinoma Adenocarcinoma of Lung Base Sequence Cell growth Cell Movement Cell Proliferation Development and progression Down-Regulation Gene expression Gene Expression Regulation, Neoplastic Genes Genetic aspects Health aspects Humans invasion lung adenocarcinoma Lung cancer Lung Neoplasms MicroRNA MicroRNAs - physiology migration miR-124 Neoplasm Invasiveness Ovarian cancer proliferation Properties Prostate RNA Interference SOX9 SOX9 Transcription Factor - genetics SOX9 Transcription Factor - metabolism Studies Superoxide dismutase |
title | miR-124 inhibits cell proliferation, migration and invasion by directly targeting SOX9 in lung adenocarcinoma |
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