Targeting of YAP1 by microRNA-15a and microRNA-16-1 exerts tumor suppressor function in gastric adenocarcinoma
MicroRNAs (miRNAs) have been reported to play an important role in tumorigenesis. In this study, the role of miR-15a and miR-16-1 in gastric adenocarcinoma (GAC) was investigated. The expression of miR-15a and miR-16-1 in cell lines and primary tumors was examined by miRNA qRT-PCR. Proliferative ass...
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| Veröffentlicht in: | Molecular cancer 2015-02, Vol.14 (1), p.52-52, Article 52 |
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| creator | Kang, Wei Tong, Joanna H M Lung, Raymond W M Dong, Yujuan Zhao, Junhong Liang, Qiaoyi Zhang, Li Pan, Yi Yang, Weiqin Pang, Jesse C S Cheng, Alfred S L Yu, Jun To, Ka Fai |
| description | MicroRNAs (miRNAs) have been reported to play an important role in tumorigenesis. In this study, the role of miR-15a and miR-16-1 in gastric adenocarcinoma (GAC) was investigated.
The expression of miR-15a and miR-16-1 in cell lines and primary tumors was examined by miRNA qRT-PCR. Proliferative assays, colony formation, cell invasion and migration, flow cytometry analysis and in vivo study were performed by ectopic expression of miR-15a and miR-16-1. The putative target genes of miR-15a and miR-16-1 were explored by TargetScan and further validated.
We found that miR-15a and miR-16-1 were down-regulated in GAC cell lines and primary tumor samples compared with normal gastric epithelium. Functional study demonstrated that ectopic expression of miR-15a and miR-16-1 suppressed cell proliferation, monolayer colony formation, invasion and migration, and xenograft formation in vivo. In addition, miR-15a and miR-16-1 induced G0/G1 cell cycle arrest which was further confirmed by Western blot and qRT-PCR of related cell cycle regulators. YAP1 was confirmed to be a functional target of miR-15a and miR-16-1 in GAC. YAP1 re-expression partly abrogated the inhibitory effect of miR-15a and miR-16-1 in GAC cells. In clinical samples, YAP1 protein expression shows negative correlation with miR-15a and miR-16-1 expression.
In conclusion, targeting YAP1 by tumor suppressor miRNA miR-15a and miR-16-1 plays inhibitory effect and this might have a therapeutic potential in GAC. |
| doi_str_mv | 10.1186/s12943-015-0323-3 |
| format | Article |
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The expression of miR-15a and miR-16-1 in cell lines and primary tumors was examined by miRNA qRT-PCR. Proliferative assays, colony formation, cell invasion and migration, flow cytometry analysis and in vivo study were performed by ectopic expression of miR-15a and miR-16-1. The putative target genes of miR-15a and miR-16-1 were explored by TargetScan and further validated.
We found that miR-15a and miR-16-1 were down-regulated in GAC cell lines and primary tumor samples compared with normal gastric epithelium. Functional study demonstrated that ectopic expression of miR-15a and miR-16-1 suppressed cell proliferation, monolayer colony formation, invasion and migration, and xenograft formation in vivo. In addition, miR-15a and miR-16-1 induced G0/G1 cell cycle arrest which was further confirmed by Western blot and qRT-PCR of related cell cycle regulators. YAP1 was confirmed to be a functional target of miR-15a and miR-16-1 in GAC. YAP1 re-expression partly abrogated the inhibitory effect of miR-15a and miR-16-1 in GAC cells. In clinical samples, YAP1 protein expression shows negative correlation with miR-15a and miR-16-1 expression.
In conclusion, targeting YAP1 by tumor suppressor miRNA miR-15a and miR-16-1 plays inhibitory effect and this might have a therapeutic potential in GAC.</description><identifier>ISSN: 1476-4598</identifier><identifier>EISSN: 1476-4598</identifier><identifier>DOI: 10.1186/s12943-015-0323-3</identifier><identifier>PMID: 25743273</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Adaptor Proteins, Signal Transducing - genetics ; Adenocarcinoma - genetics ; Animals ; Cell Line, Tumor ; Cell Movement - genetics ; Cell Proliferation - genetics ; Comparative analysis ; Development and progression ; Down-Regulation - genetics ; G1 Phase Cell Cycle Checkpoints - genetics ; Gene Expression Regulation, Neoplastic - genetics ; Genes ; Genes, Tumor Suppressor - physiology ; Genetic aspects ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; MicroRNA ; MicroRNAs - genetics ; Phosphoproteins - genetics ; Physiological aspects ; Resting Phase, Cell Cycle - genetics ; Stomach cancer ; Stomach Neoplasms - genetics ; Transcription Factors</subject><ispartof>Molecular cancer, 2015-02, Vol.14 (1), p.52-52, Article 52</ispartof><rights>COPYRIGHT 2015 BioMed Central Ltd.</rights><rights>Kang et al.; licensee BioMed Central. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c532t-c68f3bbf56e5058280f77697b9c8c0121f8d081f9c52396db04b29169d2fa2dd3</citedby><cites>FETCH-LOGICAL-c532t-c68f3bbf56e5058280f77697b9c8c0121f8d081f9c52396db04b29169d2fa2dd3</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/PMC4342823/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342823/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25743273$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kang, Wei</creatorcontrib><creatorcontrib>Tong, Joanna H M</creatorcontrib><creatorcontrib>Lung, Raymond W M</creatorcontrib><creatorcontrib>Dong, Yujuan</creatorcontrib><creatorcontrib>Zhao, Junhong</creatorcontrib><creatorcontrib>Liang, Qiaoyi</creatorcontrib><creatorcontrib>Zhang, Li</creatorcontrib><creatorcontrib>Pan, Yi</creatorcontrib><creatorcontrib>Yang, Weiqin</creatorcontrib><creatorcontrib>Pang, Jesse C S</creatorcontrib><creatorcontrib>Cheng, Alfred S L</creatorcontrib><creatorcontrib>Yu, Jun</creatorcontrib><creatorcontrib>To, Ka Fai</creatorcontrib><title>Targeting of YAP1 by microRNA-15a and microRNA-16-1 exerts tumor suppressor function in gastric adenocarcinoma</title><title>Molecular cancer</title><addtitle>Mol Cancer</addtitle><description>MicroRNAs (miRNAs) have been reported to play an important role in tumorigenesis. In this study, the role of miR-15a and miR-16-1 in gastric adenocarcinoma (GAC) was investigated.
The expression of miR-15a and miR-16-1 in cell lines and primary tumors was examined by miRNA qRT-PCR. Proliferative assays, colony formation, cell invasion and migration, flow cytometry analysis and in vivo study were performed by ectopic expression of miR-15a and miR-16-1. The putative target genes of miR-15a and miR-16-1 were explored by TargetScan and further validated.
We found that miR-15a and miR-16-1 were down-regulated in GAC cell lines and primary tumor samples compared with normal gastric epithelium. Functional study demonstrated that ectopic expression of miR-15a and miR-16-1 suppressed cell proliferation, monolayer colony formation, invasion and migration, and xenograft formation in vivo. In addition, miR-15a and miR-16-1 induced G0/G1 cell cycle arrest which was further confirmed by Western blot and qRT-PCR of related cell cycle regulators. YAP1 was confirmed to be a functional target of miR-15a and miR-16-1 in GAC. YAP1 re-expression partly abrogated the inhibitory effect of miR-15a and miR-16-1 in GAC cells. In clinical samples, YAP1 protein expression shows negative correlation with miR-15a and miR-16-1 expression.
In conclusion, targeting YAP1 by tumor suppressor miRNA miR-15a and miR-16-1 plays inhibitory effect and this might have a therapeutic potential in GAC.</description><subject>Adaptor Proteins, Signal Transducing - genetics</subject><subject>Adenocarcinoma - genetics</subject><subject>Animals</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - genetics</subject><subject>Cell Proliferation - genetics</subject><subject>Comparative analysis</subject><subject>Development and progression</subject><subject>Down-Regulation - genetics</subject><subject>G1 Phase Cell Cycle Checkpoints - genetics</subject><subject>Gene Expression Regulation, Neoplastic - genetics</subject><subject>Genes</subject><subject>Genes, Tumor Suppressor - physiology</subject><subject>Genetic aspects</subject><subject>Humans</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>MicroRNA</subject><subject>MicroRNAs - genetics</subject><subject>Phosphoproteins - genetics</subject><subject>Physiological aspects</subject><subject>Resting Phase, Cell Cycle - genetics</subject><subject>Stomach cancer</subject><subject>Stomach Neoplasms - genetics</subject><subject>Transcription Factors</subject><issn>1476-4598</issn><issn>1476-4598</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkU1rFTEUhgdR7If-ADcScOMmbb4_NsKlaBVKLaUuXIVMJhkjM8k1mRH7783l1nILkkUOJ-_7cnKernuD0RnGSpxXTDSjEGEOESUU0mfdMWZSQMa1en5QH3Untf5ECEsl2cvuiHDJKJH0uEt3tox-iWkEOYDvmxsM-nswR1fy7fUGYm6BTcNBQ0AM_B9flgqWdc4F1HW7Lb7WVoY1uSXmBGICo61LiQ7YwafsbHEx5dm-6l4EO1X_-uE-7b59-nh38Rlefb38crG5go5TskAnVKB9H7jwHHFFFApSCi177ZRDmOCgBqRw0I4TqsXQI9YTjYUeSLBkGOhp92Gfu1372Q_Op6XYyWxLnG25N9lG8_QlxR9mzL8No4woQlvA-4eAkn-tvi5mjtX5abLJ57UaLCQTGhGpm_TdXjrayZuYQm6Jbic3G84wU0px1FRn_1G1M_i23Jx8iK3_xID3hrb5WosPj9NjZHb4zR6_afjNDr_ZTf328NuPjn-86V9_Rqn0</recordid><startdate>20150222</startdate><enddate>20150222</enddate><creator>Kang, Wei</creator><creator>Tong, Joanna H M</creator><creator>Lung, Raymond W M</creator><creator>Dong, Yujuan</creator><creator>Zhao, Junhong</creator><creator>Liang, Qiaoyi</creator><creator>Zhang, Li</creator><creator>Pan, Yi</creator><creator>Yang, Weiqin</creator><creator>Pang, Jesse C S</creator><creator>Cheng, Alfred S L</creator><creator>Yu, Jun</creator><creator>To, Ka Fai</creator><general>BioMed Central Ltd</general><general>BioMed Central</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>20150222</creationdate><title>Targeting of YAP1 by microRNA-15a and microRNA-16-1 exerts tumor suppressor function in gastric adenocarcinoma</title><author>Kang, Wei ; Tong, Joanna H M ; Lung, Raymond W M ; Dong, Yujuan ; Zhao, Junhong ; Liang, Qiaoyi ; Zhang, Li ; Pan, Yi ; Yang, Weiqin ; Pang, Jesse C S ; Cheng, Alfred S L ; Yu, Jun ; To, Ka Fai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c532t-c68f3bbf56e5058280f77697b9c8c0121f8d081f9c52396db04b29169d2fa2dd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adaptor Proteins, Signal Transducing - genetics</topic><topic>Adenocarcinoma - genetics</topic><topic>Animals</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - genetics</topic><topic>Cell Proliferation - genetics</topic><topic>Comparative analysis</topic><topic>Development and progression</topic><topic>Down-Regulation - genetics</topic><topic>G1 Phase Cell Cycle Checkpoints - genetics</topic><topic>Gene Expression Regulation, Neoplastic - genetics</topic><topic>Genes</topic><topic>Genes, Tumor Suppressor - physiology</topic><topic>Genetic aspects</topic><topic>Humans</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>MicroRNA</topic><topic>MicroRNAs - genetics</topic><topic>Phosphoproteins - genetics</topic><topic>Physiological aspects</topic><topic>Resting Phase, Cell Cycle - genetics</topic><topic>Stomach cancer</topic><topic>Stomach Neoplasms - genetics</topic><topic>Transcription Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kang, Wei</creatorcontrib><creatorcontrib>Tong, Joanna H M</creatorcontrib><creatorcontrib>Lung, Raymond W M</creatorcontrib><creatorcontrib>Dong, Yujuan</creatorcontrib><creatorcontrib>Zhao, Junhong</creatorcontrib><creatorcontrib>Liang, Qiaoyi</creatorcontrib><creatorcontrib>Zhang, Li</creatorcontrib><creatorcontrib>Pan, Yi</creatorcontrib><creatorcontrib>Yang, Weiqin</creatorcontrib><creatorcontrib>Pang, Jesse C S</creatorcontrib><creatorcontrib>Cheng, Alfred S L</creatorcontrib><creatorcontrib>Yu, Jun</creatorcontrib><creatorcontrib>To, Ka Fai</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>Molecular cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kang, Wei</au><au>Tong, Joanna H M</au><au>Lung, Raymond W M</au><au>Dong, Yujuan</au><au>Zhao, Junhong</au><au>Liang, Qiaoyi</au><au>Zhang, Li</au><au>Pan, Yi</au><au>Yang, Weiqin</au><au>Pang, Jesse C S</au><au>Cheng, Alfred S L</au><au>Yu, Jun</au><au>To, Ka Fai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Targeting of YAP1 by microRNA-15a and microRNA-16-1 exerts tumor suppressor function in gastric adenocarcinoma</atitle><jtitle>Molecular cancer</jtitle><addtitle>Mol Cancer</addtitle><date>2015-02-22</date><risdate>2015</risdate><volume>14</volume><issue>1</issue><spage>52</spage><epage>52</epage><pages>52-52</pages><artnum>52</artnum><issn>1476-4598</issn><eissn>1476-4598</eissn><abstract>MicroRNAs (miRNAs) have been reported to play an important role in tumorigenesis. In this study, the role of miR-15a and miR-16-1 in gastric adenocarcinoma (GAC) was investigated.
The expression of miR-15a and miR-16-1 in cell lines and primary tumors was examined by miRNA qRT-PCR. Proliferative assays, colony formation, cell invasion and migration, flow cytometry analysis and in vivo study were performed by ectopic expression of miR-15a and miR-16-1. The putative target genes of miR-15a and miR-16-1 were explored by TargetScan and further validated.
We found that miR-15a and miR-16-1 were down-regulated in GAC cell lines and primary tumor samples compared with normal gastric epithelium. Functional study demonstrated that ectopic expression of miR-15a and miR-16-1 suppressed cell proliferation, monolayer colony formation, invasion and migration, and xenograft formation in vivo. In addition, miR-15a and miR-16-1 induced G0/G1 cell cycle arrest which was further confirmed by Western blot and qRT-PCR of related cell cycle regulators. YAP1 was confirmed to be a functional target of miR-15a and miR-16-1 in GAC. YAP1 re-expression partly abrogated the inhibitory effect of miR-15a and miR-16-1 in GAC cells. In clinical samples, YAP1 protein expression shows negative correlation with miR-15a and miR-16-1 expression.
In conclusion, targeting YAP1 by tumor suppressor miRNA miR-15a and miR-16-1 plays inhibitory effect and this might have a therapeutic potential in GAC.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>25743273</pmid><doi>10.1186/s12943-015-0323-3</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adaptor Proteins, Signal Transducing - genetics Adenocarcinoma - genetics Animals Cell Line, Tumor Cell Movement - genetics Cell Proliferation - genetics Comparative analysis Development and progression Down-Regulation - genetics G1 Phase Cell Cycle Checkpoints - genetics Gene Expression Regulation, Neoplastic - genetics Genes Genes, Tumor Suppressor - physiology Genetic aspects Humans Mice Mice, Inbred BALB C Mice, Nude MicroRNA MicroRNAs - genetics Phosphoproteins - genetics Physiological aspects Resting Phase, Cell Cycle - genetics Stomach cancer Stomach Neoplasms - genetics Transcription Factors |
| title | Targeting of YAP1 by microRNA-15a and microRNA-16-1 exerts tumor suppressor function in gastric adenocarcinoma |
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