TET3 inhibits TGF-β1-induced epithelial-mesenchymal transition by demethylating miR-30d precursor gene in ovarian cancer cells
Abnormal DNA methylation/demethylation is recognized as a hallmark of cancer. TET (ten-eleven translocation) family members are novel DNA demethylation related proteins that dysregulate in multiple malignances. However, their effects on ovarian cancer remain to be elucidated. The changes of TET fami...
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| Veröffentlicht in: | Journal of experimental & clinical cancer research 2016-05, Vol.35 (1), p.72, Article 72 |
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| creator | Ye, Zhongxue Li, Jie Han, Xi Hou, Huilian Chen, He Zheng, Xia Lu, Jiaojiao Wang, Lijie Chen, Wei Li, Xu Zhao, Le |
| description | Abnormal DNA methylation/demethylation is recognized as a hallmark of cancer. TET (ten-eleven translocation) family members are novel DNA demethylation related proteins that dysregulate in multiple malignances. However, their effects on ovarian cancer remain to be elucidated.
The changes of TET family members during TGF-β1-induced epithelial-mesenchymal transition (EMT) in SKOV3 and 3AO ovarian cancer cells were detected. TET3 was ectopically expressed in TGF-β1-treated ovarian cancer cells to examine its effect on TGF-β1-induced EMT phenotype. The downstream target of TET3 was further identified. Finally, the relationships of TET3 expression to clinic-pathological parameters of ovarian cancer were investigated with a tissue microarray using immunohistochemistry.
TET3 was downregulated during TGF-β1-initiatd epithelial-mesenchymal transition (EMT) in SKOV3 and 3AO ovarian cancer cells. Overexpression of TET3 reversed TGF-β1-induced EMT phenotypes including the expression pattern of molecular markers (E-cadherin, Vimentin, N-cadherin, Snail) and migratory and invasive capabilities of ovarian cancer cells. miR-30d was identified as a downstream target of TET3, and TET3 overexpression resumed the demethylation status in the promoter region of miR-30d precursor gene, resulting in restoration of miR-30d (an EMT suppressor of ovarian cancer cells proven in our previous study) level in TGF-β1-induced EMT. We further found that TET3 expression was decreased in ovarian cancer tissues, especially in serous ovarian cancers. The overall positivity of TET3 was inversely correlated with the grade of differentiation status of ovarian cancer.
Our results revealed that TET3 acted as a suppressor of ovarian cancer by demethylating miR-30d precursor gene promoter to block TGF-β1-induced EMT. |
| doi_str_mv | 10.1186/s13046-016-0350-y |
| format | Article |
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The changes of TET family members during TGF-β1-induced epithelial-mesenchymal transition (EMT) in SKOV3 and 3AO ovarian cancer cells were detected. TET3 was ectopically expressed in TGF-β1-treated ovarian cancer cells to examine its effect on TGF-β1-induced EMT phenotype. The downstream target of TET3 was further identified. Finally, the relationships of TET3 expression to clinic-pathological parameters of ovarian cancer were investigated with a tissue microarray using immunohistochemistry.
TET3 was downregulated during TGF-β1-initiatd epithelial-mesenchymal transition (EMT) in SKOV3 and 3AO ovarian cancer cells. Overexpression of TET3 reversed TGF-β1-induced EMT phenotypes including the expression pattern of molecular markers (E-cadherin, Vimentin, N-cadherin, Snail) and migratory and invasive capabilities of ovarian cancer cells. miR-30d was identified as a downstream target of TET3, and TET3 overexpression resumed the demethylation status in the promoter region of miR-30d precursor gene, resulting in restoration of miR-30d (an EMT suppressor of ovarian cancer cells proven in our previous study) level in TGF-β1-induced EMT. We further found that TET3 expression was decreased in ovarian cancer tissues, especially in serous ovarian cancers. The overall positivity of TET3 was inversely correlated with the grade of differentiation status of ovarian cancer.
Our results revealed that TET3 acted as a suppressor of ovarian cancer by demethylating miR-30d precursor gene promoter to block TGF-β1-induced EMT.</description><identifier>ISSN: 1756-9966</identifier><identifier>ISSN: 0392-9078</identifier><identifier>EISSN: 1756-9966</identifier><identifier>DOI: 10.1186/s13046-016-0350-y</identifier><identifier>PMID: 27141829</identifier><language>eng</language><publisher>England: BioMed Central</publisher><subject>Cell Line, Tumor ; Cell Movement - drug effects ; Dioxygenases - genetics ; Dioxygenases - metabolism ; DNA Methylation - drug effects ; Epigenesis, Genetic - drug effects ; Epithelial-Mesenchymal Transition - drug effects ; Female ; Gene Expression Regulation, Neoplastic - drug effects ; Humans ; MicroRNAs - genetics ; Ovarian Neoplasms - genetics ; Ovarian Neoplasms - metabolism ; Ovarian Neoplasms - pathology ; Promoter Regions, Genetic - drug effects ; Transforming Growth Factor beta1 - pharmacology</subject><ispartof>Journal of experimental & clinical cancer research, 2016-05, Vol.35 (1), p.72, Article 72</ispartof><rights>Ye et al. 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c399t-2375d3f0cfe040a4ed833e652b6108822d161e5f1cefa86f2e9df72619adf7ca3</citedby><cites>FETCH-LOGICAL-c399t-2375d3f0cfe040a4ed833e652b6108822d161e5f1cefa86f2e9df72619adf7ca3</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/PMC4855705/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855705/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27141829$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ye, Zhongxue</creatorcontrib><creatorcontrib>Li, Jie</creatorcontrib><creatorcontrib>Han, Xi</creatorcontrib><creatorcontrib>Hou, Huilian</creatorcontrib><creatorcontrib>Chen, He</creatorcontrib><creatorcontrib>Zheng, Xia</creatorcontrib><creatorcontrib>Lu, Jiaojiao</creatorcontrib><creatorcontrib>Wang, Lijie</creatorcontrib><creatorcontrib>Chen, Wei</creatorcontrib><creatorcontrib>Li, Xu</creatorcontrib><creatorcontrib>Zhao, Le</creatorcontrib><title>TET3 inhibits TGF-β1-induced epithelial-mesenchymal transition by demethylating miR-30d precursor gene in ovarian cancer cells</title><title>Journal of experimental & clinical cancer research</title><addtitle>J Exp Clin Cancer Res</addtitle><description>Abnormal DNA methylation/demethylation is recognized as a hallmark of cancer. TET (ten-eleven translocation) family members are novel DNA demethylation related proteins that dysregulate in multiple malignances. However, their effects on ovarian cancer remain to be elucidated.
The changes of TET family members during TGF-β1-induced epithelial-mesenchymal transition (EMT) in SKOV3 and 3AO ovarian cancer cells were detected. TET3 was ectopically expressed in TGF-β1-treated ovarian cancer cells to examine its effect on TGF-β1-induced EMT phenotype. The downstream target of TET3 was further identified. Finally, the relationships of TET3 expression to clinic-pathological parameters of ovarian cancer were investigated with a tissue microarray using immunohistochemistry.
TET3 was downregulated during TGF-β1-initiatd epithelial-mesenchymal transition (EMT) in SKOV3 and 3AO ovarian cancer cells. Overexpression of TET3 reversed TGF-β1-induced EMT phenotypes including the expression pattern of molecular markers (E-cadherin, Vimentin, N-cadherin, Snail) and migratory and invasive capabilities of ovarian cancer cells. miR-30d was identified as a downstream target of TET3, and TET3 overexpression resumed the demethylation status in the promoter region of miR-30d precursor gene, resulting in restoration of miR-30d (an EMT suppressor of ovarian cancer cells proven in our previous study) level in TGF-β1-induced EMT. We further found that TET3 expression was decreased in ovarian cancer tissues, especially in serous ovarian cancers. The overall positivity of TET3 was inversely correlated with the grade of differentiation status of ovarian cancer.
Our results revealed that TET3 acted as a suppressor of ovarian cancer by demethylating miR-30d precursor gene promoter to block TGF-β1-induced EMT.</description><subject>Cell Line, Tumor</subject><subject>Cell Movement - drug effects</subject><subject>Dioxygenases - genetics</subject><subject>Dioxygenases - metabolism</subject><subject>DNA Methylation - drug effects</subject><subject>Epigenesis, Genetic - drug effects</subject><subject>Epithelial-Mesenchymal Transition - drug effects</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Humans</subject><subject>MicroRNAs - genetics</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Ovarian Neoplasms - metabolism</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Promoter Regions, Genetic - drug effects</subject><subject>Transforming Growth Factor beta1 - pharmacology</subject><issn>1756-9966</issn><issn>0392-9078</issn><issn>1756-9966</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUdtKxDAUDKJ4Wf0AXyQ_EM1p2rR9EWTxBguCrM8hm5xuI226JN2FPvlPfojfZJdVWR8Oc-AwM8wZQi6BXwMU8iaC4KlkHMYRGWfDATmFPJOsLKU83NtPyFmM75xLKKE8JidJDikUSXlKPub3c0Gdr93C9ZHOHx_Y1ycw5-3aoKW4cn2NjdMNazGiN_XQ6ob2Qfvoetd5uhioxRb7emh07_yStu6VCW7pKqBZh9gFukSPowXtNjo47anR3mCgBpsmnpOjSjcRL35wQt4e7ufTJzZ7eXye3s2YEWXZs0TkmRUVNxXylOsUbSEEyixZSOBFkSQWJGBWgcFKF7JKsLRVnox59YhGiwm53emu1osWrUE_ZmjUKrhWh0F12qn_F-9qtew2Ki2yLOfZKAA7ARO6GANWf1zgatuG2rWhxjbUtg01jJyrfdM_xu_7xTdEBIpV</recordid><startdate>20160504</startdate><enddate>20160504</enddate><creator>Ye, Zhongxue</creator><creator>Li, Jie</creator><creator>Han, Xi</creator><creator>Hou, Huilian</creator><creator>Chen, He</creator><creator>Zheng, Xia</creator><creator>Lu, Jiaojiao</creator><creator>Wang, Lijie</creator><creator>Chen, Wei</creator><creator>Li, Xu</creator><creator>Zhao, Le</creator><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>5PM</scope></search><sort><creationdate>20160504</creationdate><title>TET3 inhibits TGF-β1-induced epithelial-mesenchymal transition by demethylating miR-30d precursor gene in ovarian cancer cells</title><author>Ye, Zhongxue ; Li, Jie ; Han, Xi ; Hou, Huilian ; Chen, He ; Zheng, Xia ; Lu, Jiaojiao ; Wang, Lijie ; Chen, Wei ; Li, Xu ; Zhao, Le</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c399t-2375d3f0cfe040a4ed833e652b6108822d161e5f1cefa86f2e9df72619adf7ca3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Cell Line, Tumor</topic><topic>Cell Movement - drug effects</topic><topic>Dioxygenases - genetics</topic><topic>Dioxygenases - metabolism</topic><topic>DNA Methylation - drug effects</topic><topic>Epigenesis, Genetic - drug effects</topic><topic>Epithelial-Mesenchymal Transition - drug effects</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Humans</topic><topic>MicroRNAs - genetics</topic><topic>Ovarian Neoplasms - genetics</topic><topic>Ovarian Neoplasms - metabolism</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Promoter Regions, Genetic - drug effects</topic><topic>Transforming Growth Factor beta1 - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ye, Zhongxue</creatorcontrib><creatorcontrib>Li, Jie</creatorcontrib><creatorcontrib>Han, Xi</creatorcontrib><creatorcontrib>Hou, Huilian</creatorcontrib><creatorcontrib>Chen, He</creatorcontrib><creatorcontrib>Zheng, Xia</creatorcontrib><creatorcontrib>Lu, Jiaojiao</creatorcontrib><creatorcontrib>Wang, Lijie</creatorcontrib><creatorcontrib>Chen, Wei</creatorcontrib><creatorcontrib>Li, Xu</creatorcontrib><creatorcontrib>Zhao, Le</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of experimental & clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ye, Zhongxue</au><au>Li, Jie</au><au>Han, Xi</au><au>Hou, Huilian</au><au>Chen, He</au><au>Zheng, Xia</au><au>Lu, Jiaojiao</au><au>Wang, Lijie</au><au>Chen, Wei</au><au>Li, Xu</au><au>Zhao, Le</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>TET3 inhibits TGF-β1-induced epithelial-mesenchymal transition by demethylating miR-30d precursor gene in ovarian cancer cells</atitle><jtitle>Journal of experimental & clinical cancer research</jtitle><addtitle>J Exp Clin Cancer Res</addtitle><date>2016-05-04</date><risdate>2016</risdate><volume>35</volume><issue>1</issue><spage>72</spage><pages>72-</pages><artnum>72</artnum><issn>1756-9966</issn><issn>0392-9078</issn><eissn>1756-9966</eissn><abstract>Abnormal DNA methylation/demethylation is recognized as a hallmark of cancer. TET (ten-eleven translocation) family members are novel DNA demethylation related proteins that dysregulate in multiple malignances. However, their effects on ovarian cancer remain to be elucidated.
The changes of TET family members during TGF-β1-induced epithelial-mesenchymal transition (EMT) in SKOV3 and 3AO ovarian cancer cells were detected. TET3 was ectopically expressed in TGF-β1-treated ovarian cancer cells to examine its effect on TGF-β1-induced EMT phenotype. The downstream target of TET3 was further identified. Finally, the relationships of TET3 expression to clinic-pathological parameters of ovarian cancer were investigated with a tissue microarray using immunohistochemistry.
TET3 was downregulated during TGF-β1-initiatd epithelial-mesenchymal transition (EMT) in SKOV3 and 3AO ovarian cancer cells. Overexpression of TET3 reversed TGF-β1-induced EMT phenotypes including the expression pattern of molecular markers (E-cadherin, Vimentin, N-cadherin, Snail) and migratory and invasive capabilities of ovarian cancer cells. miR-30d was identified as a downstream target of TET3, and TET3 overexpression resumed the demethylation status in the promoter region of miR-30d precursor gene, resulting in restoration of miR-30d (an EMT suppressor of ovarian cancer cells proven in our previous study) level in TGF-β1-induced EMT. We further found that TET3 expression was decreased in ovarian cancer tissues, especially in serous ovarian cancers. The overall positivity of TET3 was inversely correlated with the grade of differentiation status of ovarian cancer.
Our results revealed that TET3 acted as a suppressor of ovarian cancer by demethylating miR-30d precursor gene promoter to block TGF-β1-induced EMT.</abstract><cop>England</cop><pub>BioMed Central</pub><pmid>27141829</pmid><doi>10.1186/s13046-016-0350-y</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Cell Line, Tumor Cell Movement - drug effects Dioxygenases - genetics Dioxygenases - metabolism DNA Methylation - drug effects Epigenesis, Genetic - drug effects Epithelial-Mesenchymal Transition - drug effects Female Gene Expression Regulation, Neoplastic - drug effects Humans MicroRNAs - genetics Ovarian Neoplasms - genetics Ovarian Neoplasms - metabolism Ovarian Neoplasms - pathology Promoter Regions, Genetic - drug effects Transforming Growth Factor beta1 - pharmacology |
| title | TET3 inhibits TGF-β1-induced epithelial-mesenchymal transition by demethylating miR-30d precursor gene in ovarian cancer cells |
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