miR-375 is involved in Hippo pathway by targeting YAP1/TEAD4-CTGF axis in gastric carcinogenesis
miR-375 is a tumor-suppressive microRNA (miRNA) in gastric cancer (GC). However, its molecular mechanism remains unclear. The aim of this study is to comprehensively investigate how miR-375 is involved in Hippo pathway by targeting multiple oncogenes. miR-375 expression in gastric cancer cell lines...
Gespeichert in:
| Veröffentlicht in: | Cell death & disease 2018-01, Vol.9 (2), p.92-16, Article 92 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 16 |
|---|---|
| container_issue | 2 |
| container_start_page | 92 |
| container_title | Cell death & disease |
| container_volume | 9 |
| creator | Kang, Wei Huang, Tingting Zhou, Yuhang Zhang, Jinglin Lung, Raymond W. M. Tong, Joanna H. M. Chan, Anthony W. H. Zhang, Bin Wong, Chi Chun Wu, Feng Dong, Yujuan Wang, Shiyan Yang, Weiqin Pan, Yi Chak, Wing Po Cheung, Alvin H. K. Pang, Jesse C. S. Yu, Jun Cheng, Alfred S. L. To, Ka Fai |
| description | miR-375 is a tumor-suppressive microRNA (miRNA) in gastric cancer (GC). However, its molecular mechanism remains unclear. The aim of this study is to comprehensively investigate how miR-375 is involved in Hippo pathway by targeting multiple oncogenes. miR-375 expression in gastric cancer cell lines and primary GC was investigated by qRT-PCR. The regulation of YAP1, TEAD4, and CTGF expression by miR-375 was evaluated by qRT-PCR, western blot, and luciferase reporter assays, respectively. The functional roles of the related genes were examined by siRNA-mediated knockdown or ectopic expression assays. The clinical significance and expression correlation analysis of miR-375, YAP1, and CTGF were performed in primary GCs. TCGA cohort was also used to analyze the expression correlation of YAP1, TEAD4, CTGF, and miR-375 in primary GCs. miR-375 was down-regulated in GC due to promoter methylation and histone deacetylation. miR-375 downregulation was associated with unfavorable outcome and lymph node metastasis. Ectopic expression of miR-375 inhibited tumor growth in vitro and in vivo. Three components of Hippo pathway, YAP1, TEAD4 and CTGF, were revealed to be direct targets of miR-375. The expression of three genes showed a negative correlation with miR-375 expression and YAP1 re-expression partly abolished the tumor-suppressive effect of miR-375. Furthermore, CTGF was confirmed to be the key downstream of Hippo-YAP1 cascade and its knockdown phenocopied siYAP1 or miR-375 overexpression. YAP1 nuclear accumulation was positively correlated with CTGF cytoplasmic expression in primary GC tissues. Verteporfin exerted an anti-oncogenic effect in GC cell lines by quenching CTGF expression through YAP1 degradation. In short, miR-375 was involved in the Hippo pathway by targeting YAP1-TEAD4-CTGF axis and enriched our knowledge on the miRNA dysregulation in gastric tumorigenesis. |
| doi_str_mv | 10.1038/s41419-017-0134-0 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5833783</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1990840931</sourcerecordid><originalsourceid>FETCH-LOGICAL-c466t-4894edcc0c807c7e4907792e63554d098de51f9a4ae864a80cc1cccce6627bd03</originalsourceid><addsrcrecordid>eNp1UU1LAzEQDaLYUvsDvEjA89pkk90kF6HUfggFRerBU0yz6Tal3V2TbbX_3tTWUg8ODDMwb9578AC4xugOI8I7nmKKRYQwC01ohM5AM0YUR5RzcX6yN0Db-wUKRQiKk_QSNGJBUsYIa4L3lX2JCEug9dAWm3K5MVlY4MhWVQkrVc8_1RZOt7BWLje1LXL41n3GnUm_-0Cj3mQ4gOrr5xfmytfOaqiV07Yoc1MYb_0VuJippTftw2yB10F_0htF46fhY687jjRN0zoYFdRkWiPNEdPMUIEYE7FJSZLQDAmemQTPhKLK8JQqjrTGOpRJ05hNM0Ra4H7PW62nq8BkitqppaycXSm3laWy8u-lsHOZlxuZcEJY6Ba4PRC48mNtfC0X5doVwbPEQiBOkSA4oPAepV3pvTOzowJGcpeL3OciQy5yl4vcWbs5tXb8-E0hAOI9wIdTkRt3Iv0v6zebXJeL</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1990840931</pqid></control><display><type>article</type><title>miR-375 is involved in Hippo pathway by targeting YAP1/TEAD4-CTGF axis in gastric carcinogenesis</title><source>MEDLINE</source><source>Nature Free</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Springer Nature OA Free Journals</source><creator>Kang, Wei ; Huang, Tingting ; Zhou, Yuhang ; Zhang, Jinglin ; Lung, Raymond W. M. ; Tong, Joanna H. M. ; Chan, Anthony W. H. ; Zhang, Bin ; Wong, Chi Chun ; Wu, Feng ; Dong, Yujuan ; Wang, Shiyan ; Yang, Weiqin ; Pan, Yi ; Chak, Wing Po ; Cheung, Alvin H. K. ; Pang, Jesse C. S. ; Yu, Jun ; Cheng, Alfred S. L. ; To, Ka Fai</creator><creatorcontrib>Kang, Wei ; Huang, Tingting ; Zhou, Yuhang ; Zhang, Jinglin ; Lung, Raymond W. M. ; Tong, Joanna H. M. ; Chan, Anthony W. H. ; Zhang, Bin ; Wong, Chi Chun ; Wu, Feng ; Dong, Yujuan ; Wang, Shiyan ; Yang, Weiqin ; Pan, Yi ; Chak, Wing Po ; Cheung, Alvin H. K. ; Pang, Jesse C. S. ; Yu, Jun ; Cheng, Alfred S. L. ; To, Ka Fai</creatorcontrib><description>miR-375 is a tumor-suppressive microRNA (miRNA) in gastric cancer (GC). However, its molecular mechanism remains unclear. The aim of this study is to comprehensively investigate how miR-375 is involved in Hippo pathway by targeting multiple oncogenes. miR-375 expression in gastric cancer cell lines and primary GC was investigated by qRT-PCR. The regulation of YAP1, TEAD4, and CTGF expression by miR-375 was evaluated by qRT-PCR, western blot, and luciferase reporter assays, respectively. The functional roles of the related genes were examined by siRNA-mediated knockdown or ectopic expression assays. The clinical significance and expression correlation analysis of miR-375, YAP1, and CTGF were performed in primary GCs. TCGA cohort was also used to analyze the expression correlation of YAP1, TEAD4, CTGF, and miR-375 in primary GCs. miR-375 was down-regulated in GC due to promoter methylation and histone deacetylation. miR-375 downregulation was associated with unfavorable outcome and lymph node metastasis. Ectopic expression of miR-375 inhibited tumor growth in vitro and in vivo. Three components of Hippo pathway, YAP1, TEAD4 and CTGF, were revealed to be direct targets of miR-375. The expression of three genes showed a negative correlation with miR-375 expression and YAP1 re-expression partly abolished the tumor-suppressive effect of miR-375. Furthermore, CTGF was confirmed to be the key downstream of Hippo-YAP1 cascade and its knockdown phenocopied siYAP1 or miR-375 overexpression. YAP1 nuclear accumulation was positively correlated with CTGF cytoplasmic expression in primary GC tissues. Verteporfin exerted an anti-oncogenic effect in GC cell lines by quenching CTGF expression through YAP1 degradation. In short, miR-375 was involved in the Hippo pathway by targeting YAP1-TEAD4-CTGF axis and enriched our knowledge on the miRNA dysregulation in gastric tumorigenesis.</description><identifier>ISSN: 2041-4889</identifier><identifier>EISSN: 2041-4889</identifier><identifier>DOI: 10.1038/s41419-017-0134-0</identifier><identifier>PMID: 29367737</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Adaptor Proteins, Signal Transducing - metabolism ; Animals ; Antibodies ; Base Sequence ; Biochemistry ; Biomedical and Life Sciences ; Carcinogenesis ; Carcinogenesis - genetics ; Cell Biology ; Cell Culture ; Cell Line, Tumor ; Connective tissue growth factor ; Connective Tissue Growth Factor - metabolism ; Correlation analysis ; Deacetylation ; DNA methylation ; DNA-Binding Proteins - metabolism ; Down-Regulation - genetics ; Ectopic expression ; Gastric cancer ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Immunology ; Kinases ; Life Sciences ; Lymph nodes ; Metastases ; Mice, Inbred BALB C ; Mice, Nude ; MicroRNAs - genetics ; MicroRNAs - metabolism ; miRNA ; Models, Biological ; Muscle Proteins - metabolism ; Phosphoproteins - metabolism ; Protein expression ; Protein-Serine-Threonine Kinases - metabolism ; RNA, Small Interfering - metabolism ; Signal Transduction ; siRNA ; Stomach Neoplasms - genetics ; Stomach Neoplasms - pathology ; Studies ; Transcription Factors - metabolism ; Tumor cell lines ; Tumorigenesis ; Yes-associated protein</subject><ispartof>Cell death & disease, 2018-01, Vol.9 (2), p.92-16, Article 92</ispartof><rights>The Author(s) 2018</rights><rights>2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c466t-4894edcc0c807c7e4907792e63554d098de51f9a4ae864a80cc1cccce6627bd03</citedby><cites>FETCH-LOGICAL-c466t-4894edcc0c807c7e4907792e63554d098de51f9a4ae864a80cc1cccce6627bd03</cites><orcidid>0000-0003-4042-6957</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833783/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833783/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29367737$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kang, Wei</creatorcontrib><creatorcontrib>Huang, Tingting</creatorcontrib><creatorcontrib>Zhou, Yuhang</creatorcontrib><creatorcontrib>Zhang, Jinglin</creatorcontrib><creatorcontrib>Lung, Raymond W. M.</creatorcontrib><creatorcontrib>Tong, Joanna H. M.</creatorcontrib><creatorcontrib>Chan, Anthony W. H.</creatorcontrib><creatorcontrib>Zhang, Bin</creatorcontrib><creatorcontrib>Wong, Chi Chun</creatorcontrib><creatorcontrib>Wu, Feng</creatorcontrib><creatorcontrib>Dong, Yujuan</creatorcontrib><creatorcontrib>Wang, Shiyan</creatorcontrib><creatorcontrib>Yang, Weiqin</creatorcontrib><creatorcontrib>Pan, Yi</creatorcontrib><creatorcontrib>Chak, Wing Po</creatorcontrib><creatorcontrib>Cheung, Alvin H. K.</creatorcontrib><creatorcontrib>Pang, Jesse C. S.</creatorcontrib><creatorcontrib>Yu, Jun</creatorcontrib><creatorcontrib>Cheng, Alfred S. L.</creatorcontrib><creatorcontrib>To, Ka Fai</creatorcontrib><title>miR-375 is involved in Hippo pathway by targeting YAP1/TEAD4-CTGF axis in gastric carcinogenesis</title><title>Cell death & disease</title><addtitle>Cell Death Dis</addtitle><addtitle>Cell Death Dis</addtitle><description>miR-375 is a tumor-suppressive microRNA (miRNA) in gastric cancer (GC). However, its molecular mechanism remains unclear. The aim of this study is to comprehensively investigate how miR-375 is involved in Hippo pathway by targeting multiple oncogenes. miR-375 expression in gastric cancer cell lines and primary GC was investigated by qRT-PCR. The regulation of YAP1, TEAD4, and CTGF expression by miR-375 was evaluated by qRT-PCR, western blot, and luciferase reporter assays, respectively. The functional roles of the related genes were examined by siRNA-mediated knockdown or ectopic expression assays. The clinical significance and expression correlation analysis of miR-375, YAP1, and CTGF were performed in primary GCs. TCGA cohort was also used to analyze the expression correlation of YAP1, TEAD4, CTGF, and miR-375 in primary GCs. miR-375 was down-regulated in GC due to promoter methylation and histone deacetylation. miR-375 downregulation was associated with unfavorable outcome and lymph node metastasis. Ectopic expression of miR-375 inhibited tumor growth in vitro and in vivo. Three components of Hippo pathway, YAP1, TEAD4 and CTGF, were revealed to be direct targets of miR-375. The expression of three genes showed a negative correlation with miR-375 expression and YAP1 re-expression partly abolished the tumor-suppressive effect of miR-375. Furthermore, CTGF was confirmed to be the key downstream of Hippo-YAP1 cascade and its knockdown phenocopied siYAP1 or miR-375 overexpression. YAP1 nuclear accumulation was positively correlated with CTGF cytoplasmic expression in primary GC tissues. Verteporfin exerted an anti-oncogenic effect in GC cell lines by quenching CTGF expression through YAP1 degradation. In short, miR-375 was involved in the Hippo pathway by targeting YAP1-TEAD4-CTGF axis and enriched our knowledge on the miRNA dysregulation in gastric tumorigenesis.</description><subject>Adaptor Proteins, Signal Transducing - metabolism</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Base Sequence</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Carcinogenesis</subject><subject>Carcinogenesis - genetics</subject><subject>Cell Biology</subject><subject>Cell Culture</subject><subject>Cell Line, Tumor</subject><subject>Connective tissue growth factor</subject><subject>Connective Tissue Growth Factor - metabolism</subject><subject>Correlation analysis</subject><subject>Deacetylation</subject><subject>DNA methylation</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Down-Regulation - genetics</subject><subject>Ectopic expression</subject><subject>Gastric cancer</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene Knockdown Techniques</subject><subject>Humans</subject><subject>Immunology</subject><subject>Kinases</subject><subject>Life Sciences</subject><subject>Lymph nodes</subject><subject>Metastases</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>miRNA</subject><subject>Models, Biological</subject><subject>Muscle Proteins - metabolism</subject><subject>Phosphoproteins - metabolism</subject><subject>Protein expression</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Signal Transduction</subject><subject>siRNA</subject><subject>Stomach Neoplasms - genetics</subject><subject>Stomach Neoplasms - pathology</subject><subject>Studies</subject><subject>Transcription Factors - metabolism</subject><subject>Tumor cell lines</subject><subject>Tumorigenesis</subject><subject>Yes-associated protein</subject><issn>2041-4889</issn><issn>2041-4889</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1UU1LAzEQDaLYUvsDvEjA89pkk90kF6HUfggFRerBU0yz6Tal3V2TbbX_3tTWUg8ODDMwb9578AC4xugOI8I7nmKKRYQwC01ohM5AM0YUR5RzcX6yN0Db-wUKRQiKk_QSNGJBUsYIa4L3lX2JCEug9dAWm3K5MVlY4MhWVQkrVc8_1RZOt7BWLje1LXL41n3GnUm_-0Cj3mQ4gOrr5xfmytfOaqiV07Yoc1MYb_0VuJippTftw2yB10F_0htF46fhY687jjRN0zoYFdRkWiPNEdPMUIEYE7FJSZLQDAmemQTPhKLK8JQqjrTGOpRJ05hNM0Ra4H7PW62nq8BkitqppaycXSm3laWy8u-lsHOZlxuZcEJY6Ba4PRC48mNtfC0X5doVwbPEQiBOkSA4oPAepV3pvTOzowJGcpeL3OciQy5yl4vcWbs5tXb8-E0hAOI9wIdTkRt3Iv0v6zebXJeL</recordid><startdate>20180124</startdate><enddate>20180124</enddate><creator>Kang, Wei</creator><creator>Huang, Tingting</creator><creator>Zhou, Yuhang</creator><creator>Zhang, Jinglin</creator><creator>Lung, Raymond W. M.</creator><creator>Tong, Joanna H. M.</creator><creator>Chan, Anthony W. H.</creator><creator>Zhang, Bin</creator><creator>Wong, Chi Chun</creator><creator>Wu, Feng</creator><creator>Dong, Yujuan</creator><creator>Wang, Shiyan</creator><creator>Yang, Weiqin</creator><creator>Pan, Yi</creator><creator>Chak, Wing Po</creator><creator>Cheung, Alvin H. K.</creator><creator>Pang, Jesse C. S.</creator><creator>Yu, Jun</creator><creator>Cheng, Alfred S. L.</creator><creator>To, Ka Fai</creator><general>Nature Publishing Group UK</general><general>Springer Nature B.V</general><scope>C6C</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4042-6957</orcidid></search><sort><creationdate>20180124</creationdate><title>miR-375 is involved in Hippo pathway by targeting YAP1/TEAD4-CTGF axis in gastric carcinogenesis</title><author>Kang, Wei ; Huang, Tingting ; Zhou, Yuhang ; Zhang, Jinglin ; Lung, Raymond W. M. ; Tong, Joanna H. M. ; Chan, Anthony W. H. ; Zhang, Bin ; Wong, Chi Chun ; Wu, Feng ; Dong, Yujuan ; Wang, Shiyan ; Yang, Weiqin ; Pan, Yi ; Chak, Wing Po ; Cheung, Alvin H. K. ; Pang, Jesse C. S. ; Yu, Jun ; Cheng, Alfred S. L. ; To, Ka Fai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c466t-4894edcc0c807c7e4907792e63554d098de51f9a4ae864a80cc1cccce6627bd03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adaptor Proteins, Signal Transducing - metabolism</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Base Sequence</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Carcinogenesis</topic><topic>Carcinogenesis - genetics</topic><topic>Cell Biology</topic><topic>Cell Culture</topic><topic>Cell Line, Tumor</topic><topic>Connective tissue growth factor</topic><topic>Connective Tissue Growth Factor - metabolism</topic><topic>Correlation analysis</topic><topic>Deacetylation</topic><topic>DNA methylation</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Down-Regulation - genetics</topic><topic>Ectopic expression</topic><topic>Gastric cancer</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gene Knockdown Techniques</topic><topic>Humans</topic><topic>Immunology</topic><topic>Kinases</topic><topic>Life Sciences</topic><topic>Lymph nodes</topic><topic>Metastases</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>miRNA</topic><topic>Models, Biological</topic><topic>Muscle Proteins - metabolism</topic><topic>Phosphoproteins - metabolism</topic><topic>Protein expression</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>RNA, Small Interfering - metabolism</topic><topic>Signal Transduction</topic><topic>siRNA</topic><topic>Stomach Neoplasms - genetics</topic><topic>Stomach Neoplasms - pathology</topic><topic>Studies</topic><topic>Transcription Factors - metabolism</topic><topic>Tumor cell lines</topic><topic>Tumorigenesis</topic><topic>Yes-associated protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kang, Wei</creatorcontrib><creatorcontrib>Huang, Tingting</creatorcontrib><creatorcontrib>Zhou, Yuhang</creatorcontrib><creatorcontrib>Zhang, Jinglin</creatorcontrib><creatorcontrib>Lung, Raymond W. M.</creatorcontrib><creatorcontrib>Tong, Joanna H. M.</creatorcontrib><creatorcontrib>Chan, Anthony W. H.</creatorcontrib><creatorcontrib>Zhang, Bin</creatorcontrib><creatorcontrib>Wong, Chi Chun</creatorcontrib><creatorcontrib>Wu, Feng</creatorcontrib><creatorcontrib>Dong, Yujuan</creatorcontrib><creatorcontrib>Wang, Shiyan</creatorcontrib><creatorcontrib>Yang, Weiqin</creatorcontrib><creatorcontrib>Pan, Yi</creatorcontrib><creatorcontrib>Chak, Wing Po</creatorcontrib><creatorcontrib>Cheung, Alvin H. K.</creatorcontrib><creatorcontrib>Pang, Jesse C. S.</creatorcontrib><creatorcontrib>Yu, Jun</creatorcontrib><creatorcontrib>Cheng, Alfred S. L.</creatorcontrib><creatorcontrib>To, Ka Fai</creatorcontrib><collection>Springer Nature OA Free Journals</collection><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>Biology Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content 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>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell death & disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kang, Wei</au><au>Huang, Tingting</au><au>Zhou, Yuhang</au><au>Zhang, Jinglin</au><au>Lung, Raymond W. M.</au><au>Tong, Joanna H. M.</au><au>Chan, Anthony W. H.</au><au>Zhang, Bin</au><au>Wong, Chi Chun</au><au>Wu, Feng</au><au>Dong, Yujuan</au><au>Wang, Shiyan</au><au>Yang, Weiqin</au><au>Pan, Yi</au><au>Chak, Wing Po</au><au>Cheung, Alvin H. K.</au><au>Pang, Jesse C. S.</au><au>Yu, Jun</au><au>Cheng, Alfred S. L.</au><au>To, Ka Fai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>miR-375 is involved in Hippo pathway by targeting YAP1/TEAD4-CTGF axis in gastric carcinogenesis</atitle><jtitle>Cell death & disease</jtitle><stitle>Cell Death Dis</stitle><addtitle>Cell Death Dis</addtitle><date>2018-01-24</date><risdate>2018</risdate><volume>9</volume><issue>2</issue><spage>92</spage><epage>16</epage><pages>92-16</pages><artnum>92</artnum><issn>2041-4889</issn><eissn>2041-4889</eissn><abstract>miR-375 is a tumor-suppressive microRNA (miRNA) in gastric cancer (GC). However, its molecular mechanism remains unclear. The aim of this study is to comprehensively investigate how miR-375 is involved in Hippo pathway by targeting multiple oncogenes. miR-375 expression in gastric cancer cell lines and primary GC was investigated by qRT-PCR. The regulation of YAP1, TEAD4, and CTGF expression by miR-375 was evaluated by qRT-PCR, western blot, and luciferase reporter assays, respectively. The functional roles of the related genes were examined by siRNA-mediated knockdown or ectopic expression assays. The clinical significance and expression correlation analysis of miR-375, YAP1, and CTGF were performed in primary GCs. TCGA cohort was also used to analyze the expression correlation of YAP1, TEAD4, CTGF, and miR-375 in primary GCs. miR-375 was down-regulated in GC due to promoter methylation and histone deacetylation. miR-375 downregulation was associated with unfavorable outcome and lymph node metastasis. Ectopic expression of miR-375 inhibited tumor growth in vitro and in vivo. Three components of Hippo pathway, YAP1, TEAD4 and CTGF, were revealed to be direct targets of miR-375. The expression of three genes showed a negative correlation with miR-375 expression and YAP1 re-expression partly abolished the tumor-suppressive effect of miR-375. Furthermore, CTGF was confirmed to be the key downstream of Hippo-YAP1 cascade and its knockdown phenocopied siYAP1 or miR-375 overexpression. YAP1 nuclear accumulation was positively correlated with CTGF cytoplasmic expression in primary GC tissues. Verteporfin exerted an anti-oncogenic effect in GC cell lines by quenching CTGF expression through YAP1 degradation. In short, miR-375 was involved in the Hippo pathway by targeting YAP1-TEAD4-CTGF axis and enriched our knowledge on the miRNA dysregulation in gastric tumorigenesis.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>29367737</pmid><doi>10.1038/s41419-017-0134-0</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0003-4042-6957</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2041-4889 |
| ispartof | Cell death & disease, 2018-01, Vol.9 (2), p.92-16, Article 92 |
| issn | 2041-4889 2041-4889 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5833783 |
| source | MEDLINE; Nature Free; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Springer Nature OA Free Journals |
| subjects | Adaptor Proteins, Signal Transducing - metabolism Animals Antibodies Base Sequence Biochemistry Biomedical and Life Sciences Carcinogenesis Carcinogenesis - genetics Cell Biology Cell Culture Cell Line, Tumor Connective tissue growth factor Connective Tissue Growth Factor - metabolism Correlation analysis Deacetylation DNA methylation DNA-Binding Proteins - metabolism Down-Regulation - genetics Ectopic expression Gastric cancer Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Humans Immunology Kinases Life Sciences Lymph nodes Metastases Mice, Inbred BALB C Mice, Nude MicroRNAs - genetics MicroRNAs - metabolism miRNA Models, Biological Muscle Proteins - metabolism Phosphoproteins - metabolism Protein expression Protein-Serine-Threonine Kinases - metabolism RNA, Small Interfering - metabolism Signal Transduction siRNA Stomach Neoplasms - genetics Stomach Neoplasms - pathology Studies Transcription Factors - metabolism Tumor cell lines Tumorigenesis Yes-associated protein |
| title | miR-375 is involved in Hippo pathway by targeting YAP1/TEAD4-CTGF axis in gastric carcinogenesis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T11%3A31%3A30IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=miR-375%20is%20involved%20in%20Hippo%20pathway%20by%20targeting%20YAP1/TEAD4-CTGF%20axis%20in%20gastric%20carcinogenesis&rft.jtitle=Cell%20death%20&%20disease&rft.au=Kang,%20Wei&rft.date=2018-01-24&rft.volume=9&rft.issue=2&rft.spage=92&rft.epage=16&rft.pages=92-16&rft.artnum=92&rft.issn=2041-4889&rft.eissn=2041-4889&rft_id=info:doi/10.1038/s41419-017-0134-0&rft_dat=%3Cproquest_pubme%3E1990840931%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1990840931&rft_id=info:pmid/29367737&rfr_iscdi=true |