miR-146a functions as a tumor suppressor in prostate cancer by targeting Rac1
ABSTRACT BACKGROUND miR‐146a (miR‐146a‐5p) has been reported to be aberrantly expressed in different types of cancers, the current knowledge about the role of miR‐146a in prostate cancer is still limited. METHODS The expression levels of miR‐146a in cell lines and tissues were measured by qRT‐PCR an...
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| Veröffentlicht in: | The Prostate 2014-12, Vol.74 (16), p.1613-1621 |
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| container_title | The Prostate |
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| creator | Sun, Qian Zhao, Xian Liu, Xin Wang, Yanli Huang, Jian Jiang, Bing Chen, Qin Yu, Jianxiu |
| description | ABSTRACT
BACKGROUND
miR‐146a (miR‐146a‐5p) has been reported to be aberrantly expressed in different types of cancers, the current knowledge about the role of miR‐146a in prostate cancer is still limited.
METHODS
The expression levels of miR‐146a in cell lines and tissues were measured by qRT‐PCR and in situ hybridization. Effects of miR‐146a on cell growth and migration were evaluated by colony formation assay and RTCA assay, respectively. The dual luciferase assay was used to examine the binding between miR‐146a and the 3'UTR of potential targets.
RESULTS
We found that enforced over‐expression of miR‐146a in prostate cancer cells suppressed whereas knockdown of miR‐146a increased anchorage‐independent growth, migration, and invasion. Mechanistic studies revealed that miR‐146a repressed the expression of Rac1 through binding to its 3'UTR. Consistently, knockdown of Rac1 phenocopied the anti‐migration effect of overexpressing miR‐146a, and knockdown of Rac1 in miR‐146a‐silencing cells antagonized the increase in cell motility induced by silencing miR‐146a. Furthermore, miR‐146a was found to be inversely correlated with Rac1 in human prostate cancer tissues.
CONCLUSIONS
Our data suggest that miR‐146a plays a suppressive role in prostate cancer through down‐regulation of Rac1. The miR‐146a/Rac1 signaling axis may be a potential therapeutic target to prevent prostate cancer progression. Prostate 74: 1613–1621, 2014. © 2014 Wiley Periodicals, Inc. |
| doi_str_mv | 10.1002/pros.22878 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_1635036156</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3464336081</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5298-cdd412f10d743acd2ed620ef47734638ccc36731e05cb97c2e2251b93e8c6ab33</originalsourceid><addsrcrecordid>eNqNkU1PGzEQhi1UBCHthR-ALPXCZcN4_LV7bFEJSHwpbVUpF8vrddDS7G5q7wry73FI4NAT0kgeyc879vsOIccMJgwAz1ahixPEXOd7ZMSg0BmAkJ_ICFBDJhjXh-QoxkeAhAMekEOUyARwOSI3TT3LmFCWLobW9XXXRmpT0X5oukDjsFoFH2Nq65ZuHupt76mzrfOBlmva2_Dg-7p9oDPr2Geyv7DL6L_szjH5ffHj1_lldn03vTr_dp05iUWeuaoSDBcMKi24dRX6SiH4hdCaC8Vz5xxXmjMP0pWFdugRJSsL7nOnbMn5mJxu56Yf_Rt87E1TR-eXS9v6boiGKS6BKybVB9DkvkCV4hiTr_-hj90Q2mRkQ3GBSiIm6mRHDWXjK7MKdWPD2rxlmgC2BZ7qpV-_3zMwm22ZTYjmdVvmfnb387VLmmyrqWPvn981Nvw1KQgtzZ_bqZlzdsPn33NT8Bdb65Px</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1613426522</pqid></control><display><type>article</type><title>miR-146a functions as a tumor suppressor in prostate cancer by targeting Rac1</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Sun, Qian ; Zhao, Xian ; Liu, Xin ; Wang, Yanli ; Huang, Jian ; Jiang, Bing ; Chen, Qin ; Yu, Jianxiu</creator><creatorcontrib>Sun, Qian ; Zhao, Xian ; Liu, Xin ; Wang, Yanli ; Huang, Jian ; Jiang, Bing ; Chen, Qin ; Yu, Jianxiu</creatorcontrib><description>ABSTRACT
BACKGROUND
miR‐146a (miR‐146a‐5p) has been reported to be aberrantly expressed in different types of cancers, the current knowledge about the role of miR‐146a in prostate cancer is still limited.
METHODS
The expression levels of miR‐146a in cell lines and tissues were measured by qRT‐PCR and in situ hybridization. Effects of miR‐146a on cell growth and migration were evaluated by colony formation assay and RTCA assay, respectively. The dual luciferase assay was used to examine the binding between miR‐146a and the 3'UTR of potential targets.
RESULTS
We found that enforced over‐expression of miR‐146a in prostate cancer cells suppressed whereas knockdown of miR‐146a increased anchorage‐independent growth, migration, and invasion. Mechanistic studies revealed that miR‐146a repressed the expression of Rac1 through binding to its 3'UTR. Consistently, knockdown of Rac1 phenocopied the anti‐migration effect of overexpressing miR‐146a, and knockdown of Rac1 in miR‐146a‐silencing cells antagonized the increase in cell motility induced by silencing miR‐146a. Furthermore, miR‐146a was found to be inversely correlated with Rac1 in human prostate cancer tissues.
CONCLUSIONS
Our data suggest that miR‐146a plays a suppressive role in prostate cancer through down‐regulation of Rac1. The miR‐146a/Rac1 signaling axis may be a potential therapeutic target to prevent prostate cancer progression. Prostate 74: 1613–1621, 2014. © 2014 Wiley Periodicals, Inc.</description><identifier>ISSN: 0270-4137</identifier><identifier>EISSN: 1097-0045</identifier><identifier>DOI: 10.1002/pros.22878</identifier><identifier>PMID: 25214035</identifier><identifier>CODEN: PRSTDS</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Cell Line, Tumor ; Cell Movement - physiology ; Cell Proliferation - physiology ; Down-Regulation - physiology ; Gene Expression Regulation, Neoplastic - genetics ; Gene Expression Regulation, Neoplastic - physiology ; Gene Silencing ; Genes, Tumor Suppressor - physiology ; Humans ; Male ; MicroRNAs - drug effects ; MicroRNAs - genetics ; MicroRNAs - physiology ; miR-146a ; prostate cancer ; Prostatic Neoplasms - pathology ; Rac1 ; rac1 GTP-Binding Protein - physiology ; RNA, Small Interfering - pharmacology ; Signal Transduction - physiology ; tumor metastasis</subject><ispartof>The Prostate, 2014-12, Vol.74 (16), p.1613-1621</ispartof><rights>2014 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5298-cdd412f10d743acd2ed620ef47734638ccc36731e05cb97c2e2251b93e8c6ab33</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpros.22878$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpros.22878$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25214035$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sun, Qian</creatorcontrib><creatorcontrib>Zhao, Xian</creatorcontrib><creatorcontrib>Liu, Xin</creatorcontrib><creatorcontrib>Wang, Yanli</creatorcontrib><creatorcontrib>Huang, Jian</creatorcontrib><creatorcontrib>Jiang, Bing</creatorcontrib><creatorcontrib>Chen, Qin</creatorcontrib><creatorcontrib>Yu, Jianxiu</creatorcontrib><title>miR-146a functions as a tumor suppressor in prostate cancer by targeting Rac1</title><title>The Prostate</title><addtitle>Prostate</addtitle><description>ABSTRACT
BACKGROUND
miR‐146a (miR‐146a‐5p) has been reported to be aberrantly expressed in different types of cancers, the current knowledge about the role of miR‐146a in prostate cancer is still limited.
METHODS
The expression levels of miR‐146a in cell lines and tissues were measured by qRT‐PCR and in situ hybridization. Effects of miR‐146a on cell growth and migration were evaluated by colony formation assay and RTCA assay, respectively. The dual luciferase assay was used to examine the binding between miR‐146a and the 3'UTR of potential targets.
RESULTS
We found that enforced over‐expression of miR‐146a in prostate cancer cells suppressed whereas knockdown of miR‐146a increased anchorage‐independent growth, migration, and invasion. Mechanistic studies revealed that miR‐146a repressed the expression of Rac1 through binding to its 3'UTR. Consistently, knockdown of Rac1 phenocopied the anti‐migration effect of overexpressing miR‐146a, and knockdown of Rac1 in miR‐146a‐silencing cells antagonized the increase in cell motility induced by silencing miR‐146a. Furthermore, miR‐146a was found to be inversely correlated with Rac1 in human prostate cancer tissues.
CONCLUSIONS
Our data suggest that miR‐146a plays a suppressive role in prostate cancer through down‐regulation of Rac1. The miR‐146a/Rac1 signaling axis may be a potential therapeutic target to prevent prostate cancer progression. Prostate 74: 1613–1621, 2014. © 2014 Wiley Periodicals, Inc.</description><subject>Cell Line, Tumor</subject><subject>Cell Movement - physiology</subject><subject>Cell Proliferation - physiology</subject><subject>Down-Regulation - physiology</subject><subject>Gene Expression Regulation, Neoplastic - genetics</subject><subject>Gene Expression Regulation, Neoplastic - physiology</subject><subject>Gene Silencing</subject><subject>Genes, Tumor Suppressor - physiology</subject><subject>Humans</subject><subject>Male</subject><subject>MicroRNAs - drug effects</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - physiology</subject><subject>miR-146a</subject><subject>prostate cancer</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Rac1</subject><subject>rac1 GTP-Binding Protein - physiology</subject><subject>RNA, Small Interfering - pharmacology</subject><subject>Signal Transduction - physiology</subject><subject>tumor metastasis</subject><issn>0270-4137</issn><issn>1097-0045</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1PGzEQhi1UBCHthR-ALPXCZcN4_LV7bFEJSHwpbVUpF8vrddDS7G5q7wry73FI4NAT0kgeyc879vsOIccMJgwAz1ahixPEXOd7ZMSg0BmAkJ_ICFBDJhjXh-QoxkeAhAMekEOUyARwOSI3TT3LmFCWLobW9XXXRmpT0X5oukDjsFoFH2Nq65ZuHupt76mzrfOBlmva2_Dg-7p9oDPr2Geyv7DL6L_szjH5ffHj1_lldn03vTr_dp05iUWeuaoSDBcMKi24dRX6SiH4hdCaC8Vz5xxXmjMP0pWFdugRJSsL7nOnbMn5mJxu56Yf_Rt87E1TR-eXS9v6boiGKS6BKybVB9DkvkCV4hiTr_-hj90Q2mRkQ3GBSiIm6mRHDWXjK7MKdWPD2rxlmgC2BZ7qpV-_3zMwm22ZTYjmdVvmfnb387VLmmyrqWPvn981Nvw1KQgtzZ_bqZlzdsPn33NT8Bdb65Px</recordid><startdate>201412</startdate><enddate>201412</enddate><creator>Sun, Qian</creator><creator>Zhao, Xian</creator><creator>Liu, Xin</creator><creator>Wang, Yanli</creator><creator>Huang, Jian</creator><creator>Jiang, Bing</creator><creator>Chen, Qin</creator><creator>Yu, Jianxiu</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7T5</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201412</creationdate><title>miR-146a functions as a tumor suppressor in prostate cancer by targeting Rac1</title><author>Sun, Qian ; Zhao, Xian ; Liu, Xin ; Wang, Yanli ; Huang, Jian ; Jiang, Bing ; Chen, Qin ; Yu, Jianxiu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5298-cdd412f10d743acd2ed620ef47734638ccc36731e05cb97c2e2251b93e8c6ab33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Cell Line, Tumor</topic><topic>Cell Movement - physiology</topic><topic>Cell Proliferation - physiology</topic><topic>Down-Regulation - physiology</topic><topic>Gene Expression Regulation, Neoplastic - genetics</topic><topic>Gene Expression Regulation, Neoplastic - physiology</topic><topic>Gene Silencing</topic><topic>Genes, Tumor Suppressor - physiology</topic><topic>Humans</topic><topic>Male</topic><topic>MicroRNAs - drug effects</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - physiology</topic><topic>miR-146a</topic><topic>prostate cancer</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Rac1</topic><topic>rac1 GTP-Binding Protein - physiology</topic><topic>RNA, Small Interfering - pharmacology</topic><topic>Signal Transduction - physiology</topic><topic>tumor metastasis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sun, Qian</creatorcontrib><creatorcontrib>Zhao, Xian</creatorcontrib><creatorcontrib>Liu, Xin</creatorcontrib><creatorcontrib>Wang, Yanli</creatorcontrib><creatorcontrib>Huang, Jian</creatorcontrib><creatorcontrib>Jiang, Bing</creatorcontrib><creatorcontrib>Chen, Qin</creatorcontrib><creatorcontrib>Yu, Jianxiu</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Prostate</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sun, Qian</au><au>Zhao, Xian</au><au>Liu, Xin</au><au>Wang, Yanli</au><au>Huang, Jian</au><au>Jiang, Bing</au><au>Chen, Qin</au><au>Yu, Jianxiu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>miR-146a functions as a tumor suppressor in prostate cancer by targeting Rac1</atitle><jtitle>The Prostate</jtitle><addtitle>Prostate</addtitle><date>2014-12</date><risdate>2014</risdate><volume>74</volume><issue>16</issue><spage>1613</spage><epage>1621</epage><pages>1613-1621</pages><issn>0270-4137</issn><eissn>1097-0045</eissn><coden>PRSTDS</coden><abstract>ABSTRACT
BACKGROUND
miR‐146a (miR‐146a‐5p) has been reported to be aberrantly expressed in different types of cancers, the current knowledge about the role of miR‐146a in prostate cancer is still limited.
METHODS
The expression levels of miR‐146a in cell lines and tissues were measured by qRT‐PCR and in situ hybridization. Effects of miR‐146a on cell growth and migration were evaluated by colony formation assay and RTCA assay, respectively. The dual luciferase assay was used to examine the binding between miR‐146a and the 3'UTR of potential targets.
RESULTS
We found that enforced over‐expression of miR‐146a in prostate cancer cells suppressed whereas knockdown of miR‐146a increased anchorage‐independent growth, migration, and invasion. Mechanistic studies revealed that miR‐146a repressed the expression of Rac1 through binding to its 3'UTR. Consistently, knockdown of Rac1 phenocopied the anti‐migration effect of overexpressing miR‐146a, and knockdown of Rac1 in miR‐146a‐silencing cells antagonized the increase in cell motility induced by silencing miR‐146a. Furthermore, miR‐146a was found to be inversely correlated with Rac1 in human prostate cancer tissues.
CONCLUSIONS
Our data suggest that miR‐146a plays a suppressive role in prostate cancer through down‐regulation of Rac1. The miR‐146a/Rac1 signaling axis may be a potential therapeutic target to prevent prostate cancer progression. Prostate 74: 1613–1621, 2014. © 2014 Wiley Periodicals, Inc.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>25214035</pmid><doi>10.1002/pros.22878</doi><tpages>9</tpages></addata></record> |
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| subjects | Cell Line, Tumor Cell Movement - physiology Cell Proliferation - physiology Down-Regulation - physiology Gene Expression Regulation, Neoplastic - genetics Gene Expression Regulation, Neoplastic - physiology Gene Silencing Genes, Tumor Suppressor - physiology Humans Male MicroRNAs - drug effects MicroRNAs - genetics MicroRNAs - physiology miR-146a prostate cancer Prostatic Neoplasms - pathology Rac1 rac1 GTP-Binding Protein - physiology RNA, Small Interfering - pharmacology Signal Transduction - physiology tumor metastasis |
| title | miR-146a functions as a tumor suppressor in prostate cancer by targeting Rac1 |
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