Microarray Profiling of TGF-β1-Induced Long Non-Coding RNA Expression Patterns in Human Lung Bronchial Epithelial BEAS-2B Cells
Background/Aims: TGF-β1 mediated radiation-induced bystander effects (RIBE) have been linked with malignant transformation and tumorigenesis. However, the underlying mechanisms are not fully understood. Methods: To reveal new molecules of regulatory functions in this process, lncRNA microarray was p...
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| Veröffentlicht in: | Cellular physiology and biochemistry 2018-11, Vol.50 (6), p.2071-2085 |
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| creator | Hu, Wentao Pei, Weiwei Zhu, Lin Nie, Jing Pei, Hailong Zhang, Jian Li, Bingyan Hei, Tom K. Zhou, Guangming |
| description | Background/Aims: TGF-β1 mediated radiation-induced bystander effects (RIBE) have been linked with malignant transformation and tumorigenesis. However, the underlying mechanisms are not fully understood. Methods: To reveal new molecules of regulatory functions in this process, lncRNA microarray was performed to profile both lncRNA and mRNA expression patterns in human lung bronchial epithelial BEAS-2B cells treated with TGF-β1 at a concentration measured in the medium conditioned by directly irradiated BEAS-2B cells. The potential functions of the differentially expressed lncRNAs were predicted by GO and KEGG pathway analyses of their co-expressed mRNAs. Cis- and trans-regulation of the lncRNAs were analyzed and the interaction networks were constructed using Cytoscape. qRT-PCR was conducted to validate the results of microarray profiling. CCK-8 assay was employed for functional validation of 3 identified lncRNAs. Results: 224 lncRNAs were found to be dysregulated, among which 6 lncRNAs were chosen for expression validation by qRT-PCR assay. Pathway analyses showed that differentially expressed lncRNAs are highly correlated with cell proliferation, transformation, migration, etc. Trans-regulation analyses showed that the differentially expressed lncRNAs most likely participate in the pathways regulated by four transcriptional factors, FOS, STAT3, RAD21 and E2F1, which have been identified to be involved in the modulation of oncogenic transformation, cell cycle progression, genomic instability, etc. lnc-THEMIS-2 and lnc-ITGB6-4, predicted to be regulated by STAT3 and E2F1 respectively, were found to rescue the decrease of cell viability induced by TGF-β1 treatment. Conclusion: Our findings suggest that the differentially expressed lncRNAs induced by TGF-β1 play crucial roles in the oncogenic transformation and tumorigenesis, which provide a better understanding of the underlying mechanisms related to tumorigensis induced by LD/LDR radiations. |
| doi_str_mv | 10.1159/000495052 |
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However, the underlying mechanisms are not fully understood. Methods: To reveal new molecules of regulatory functions in this process, lncRNA microarray was performed to profile both lncRNA and mRNA expression patterns in human lung bronchial epithelial BEAS-2B cells treated with TGF-β1 at a concentration measured in the medium conditioned by directly irradiated BEAS-2B cells. The potential functions of the differentially expressed lncRNAs were predicted by GO and KEGG pathway analyses of their co-expressed mRNAs. Cis- and trans-regulation of the lncRNAs were analyzed and the interaction networks were constructed using Cytoscape. qRT-PCR was conducted to validate the results of microarray profiling. CCK-8 assay was employed for functional validation of 3 identified lncRNAs. Results: 224 lncRNAs were found to be dysregulated, among which 6 lncRNAs were chosen for expression validation by qRT-PCR assay. Pathway analyses showed that differentially expressed lncRNAs are highly correlated with cell proliferation, transformation, migration, etc. Trans-regulation analyses showed that the differentially expressed lncRNAs most likely participate in the pathways regulated by four transcriptional factors, FOS, STAT3, RAD21 and E2F1, which have been identified to be involved in the modulation of oncogenic transformation, cell cycle progression, genomic instability, etc. lnc-THEMIS-2 and lnc-ITGB6-4, predicted to be regulated by STAT3 and E2F1 respectively, were found to rescue the decrease of cell viability induced by TGF-β1 treatment. Conclusion: Our findings suggest that the differentially expressed lncRNAs induced by TGF-β1 play crucial roles in the oncogenic transformation and tumorigenesis, which provide a better understanding of the underlying mechanisms related to tumorigensis induced by LD/LDR radiations.</description><identifier>ISSN: 1015-8987</identifier><identifier>EISSN: 1421-9778</identifier><identifier>DOI: 10.1159/000495052</identifier><identifier>PMID: 30423581</identifier><language>eng</language><publisher>Basel, Switzerland: S. Karger AG</publisher><subject>BEAS-2B ; Bronchi - cytology ; Cancer therapies ; Cell Line ; Cytokines ; Down-Regulation - drug effects ; Epithelial Cells - cytology ; Epithelial Cells - drug effects ; Epithelial Cells - metabolism ; Epithelial-Mesenchymal Transition - drug effects ; Fibronectins - metabolism ; Gene expression ; Gene Expression Profiling ; Gene Regulatory Networks - genetics ; Genomes ; Growth factors ; Humans ; Long non-coding RNA ; Microarray ; Original Paper ; Proto-Oncogene Proteins c-fos - genetics ; Proto-Oncogene Proteins c-fos - metabolism ; Radiation therapy ; RNA Interference ; RNA, Long Noncoding - antagonists & inhibitors ; RNA, Long Noncoding - genetics ; RNA, Long Noncoding - metabolism ; RNA, Messenger - metabolism ; RNA, Small Interfering - metabolism ; STAT3 Transcription Factor - genetics ; STAT3 Transcription Factor - metabolism ; TGF-β1 ; Transcriptome - drug effects ; Transforming Growth Factor beta1 - pharmacology ; Tumorigenesis ; Up-Regulation - drug effects</subject><ispartof>Cellular physiology and biochemistry, 2018-11, Vol.50 (6), p.2071-2085</ispartof><rights>2018 The Author(s). Published by S. Karger AG, Basel</rights><rights>2018 The Author(s). Published by S. Karger AG, Basel.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3782-931c62924b22b16ebe81e281b37c493575a8c74e2a63c3e8fc72f6df31530b1f3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,860,2095,27614,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30423581$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hu, Wentao</creatorcontrib><creatorcontrib>Pei, Weiwei</creatorcontrib><creatorcontrib>Zhu, Lin</creatorcontrib><creatorcontrib>Nie, Jing</creatorcontrib><creatorcontrib>Pei, Hailong</creatorcontrib><creatorcontrib>Zhang, Jian</creatorcontrib><creatorcontrib>Li, Bingyan</creatorcontrib><creatorcontrib>Hei, Tom K.</creatorcontrib><creatorcontrib>Zhou, Guangming</creatorcontrib><title>Microarray Profiling of TGF-β1-Induced Long Non-Coding RNA Expression Patterns in Human Lung Bronchial Epithelial BEAS-2B Cells</title><title>Cellular physiology and biochemistry</title><addtitle>Cell Physiol Biochem</addtitle><description>Background/Aims: TGF-β1 mediated radiation-induced bystander effects (RIBE) have been linked with malignant transformation and tumorigenesis. However, the underlying mechanisms are not fully understood. Methods: To reveal new molecules of regulatory functions in this process, lncRNA microarray was performed to profile both lncRNA and mRNA expression patterns in human lung bronchial epithelial BEAS-2B cells treated with TGF-β1 at a concentration measured in the medium conditioned by directly irradiated BEAS-2B cells. The potential functions of the differentially expressed lncRNAs were predicted by GO and KEGG pathway analyses of their co-expressed mRNAs. Cis- and trans-regulation of the lncRNAs were analyzed and the interaction networks were constructed using Cytoscape. qRT-PCR was conducted to validate the results of microarray profiling. CCK-8 assay was employed for functional validation of 3 identified lncRNAs. Results: 224 lncRNAs were found to be dysregulated, among which 6 lncRNAs were chosen for expression validation by qRT-PCR assay. Pathway analyses showed that differentially expressed lncRNAs are highly correlated with cell proliferation, transformation, migration, etc. Trans-regulation analyses showed that the differentially expressed lncRNAs most likely participate in the pathways regulated by four transcriptional factors, FOS, STAT3, RAD21 and E2F1, which have been identified to be involved in the modulation of oncogenic transformation, cell cycle progression, genomic instability, etc. lnc-THEMIS-2 and lnc-ITGB6-4, predicted to be regulated by STAT3 and E2F1 respectively, were found to rescue the decrease of cell viability induced by TGF-β1 treatment. Conclusion: Our findings suggest that the differentially expressed lncRNAs induced by TGF-β1 play crucial roles in the oncogenic transformation and tumorigenesis, which provide a better understanding of the underlying mechanisms related to tumorigensis induced by LD/LDR radiations.</description><subject>BEAS-2B</subject><subject>Bronchi - cytology</subject><subject>Cancer therapies</subject><subject>Cell Line</subject><subject>Cytokines</subject><subject>Down-Regulation - drug effects</subject><subject>Epithelial Cells - cytology</subject><subject>Epithelial Cells - drug effects</subject><subject>Epithelial Cells - metabolism</subject><subject>Epithelial-Mesenchymal Transition - drug effects</subject><subject>Fibronectins - metabolism</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Regulatory Networks - genetics</subject><subject>Genomes</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Long non-coding RNA</subject><subject>Microarray</subject><subject>Original Paper</subject><subject>Proto-Oncogene Proteins c-fos - genetics</subject><subject>Proto-Oncogene Proteins c-fos - metabolism</subject><subject>Radiation therapy</subject><subject>RNA Interference</subject><subject>RNA, Long Noncoding - antagonists & inhibitors</subject><subject>RNA, Long Noncoding - genetics</subject><subject>RNA, Long Noncoding - metabolism</subject><subject>RNA, Messenger - metabolism</subject><subject>RNA, Small Interfering - metabolism</subject><subject>STAT3 Transcription Factor - genetics</subject><subject>STAT3 Transcription Factor - metabolism</subject><subject>TGF-β1</subject><subject>Transcriptome - drug effects</subject><subject>Transforming Growth Factor beta1 - pharmacology</subject><subject>Tumorigenesis</subject><subject>Up-Regulation - drug effects</subject><issn>1015-8987</issn><issn>1421-9778</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>M--</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DOA</sourceid><recordid>eNptkc9u1DAQxiMEoqVw4I6QpV7gEPDf2D7uRtt2paWsoJwtx3G2XrJxsBOJ3vpMfRCeCS8pOSBOHs_85tPMfFn2GsEPCDH5EUJIJYMMP8lOEcUol5yLpymGiOVCCn6SvYhxD9OXS_w8OyGQYsIEOs3uPzkTvA5B34Ft8I1rXbcDvgE3lxf5rweUr7t6NLYGG5_y177LS18fkS_XC7D62Qcbo_Md2OphsKGLwHXgajzoDmzGRC2D78yt0y1Y9W64te0xXK4WX3O8BKVt2_gye9boNtpXj-9Z9u1idVNe5ZvPl-tysckN4QLnkiBTYIlphXGFCltZgSwWqCLcUEkYZ1oYTi3WBTHEisZw3BR1QxAjsEINOcvWk27t9V71wR10uFNeO_Un4cNO6TA401olhbZYGiaMkBRRVBUMplNCYjhjhTZJ692k1Qf_Y7RxUAcXTdpGd9aPUWFECCUFZiyh5_-gez-GLm2qMIFIQlIgmqj3E5W8iDHYZh4QQXW0WM0WJ_bto-JYHWw9k389TcCbCfiuw86GGZj7z_9bLrfLiVB9OttvdaCx4g</recordid><startdate>20181101</startdate><enddate>20181101</enddate><creator>Hu, Wentao</creator><creator>Pei, Weiwei</creator><creator>Zhu, Lin</creator><creator>Nie, Jing</creator><creator>Pei, Hailong</creator><creator>Zhang, Jian</creator><creator>Li, Bingyan</creator><creator>Hei, Tom K.</creator><creator>Zhou, Guangming</creator><general>S. Karger AG</general><general>Cell Physiol Biochem Press GmbH & Co KG</general><scope>M--</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>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</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><scope>DOA</scope></search><sort><creationdate>20181101</creationdate><title>Microarray Profiling of TGF-β1-Induced Long Non-Coding RNA Expression Patterns in Human Lung Bronchial Epithelial BEAS-2B Cells</title><author>Hu, Wentao ; Pei, Weiwei ; Zhu, Lin ; Nie, Jing ; Pei, Hailong ; Zhang, Jian ; Li, Bingyan ; Hei, Tom K. ; Zhou, Guangming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3782-931c62924b22b16ebe81e281b37c493575a8c74e2a63c3e8fc72f6df31530b1f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>BEAS-2B</topic><topic>Bronchi - cytology</topic><topic>Cancer therapies</topic><topic>Cell Line</topic><topic>Cytokines</topic><topic>Down-Regulation - drug effects</topic><topic>Epithelial Cells - cytology</topic><topic>Epithelial Cells - drug effects</topic><topic>Epithelial Cells - metabolism</topic><topic>Epithelial-Mesenchymal Transition - drug effects</topic><topic>Fibronectins - metabolism</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Gene Regulatory Networks - genetics</topic><topic>Genomes</topic><topic>Growth factors</topic><topic>Humans</topic><topic>Long non-coding RNA</topic><topic>Microarray</topic><topic>Original Paper</topic><topic>Proto-Oncogene Proteins c-fos - genetics</topic><topic>Proto-Oncogene Proteins c-fos - metabolism</topic><topic>Radiation therapy</topic><topic>RNA Interference</topic><topic>RNA, Long Noncoding - antagonists & inhibitors</topic><topic>RNA, Long Noncoding - genetics</topic><topic>RNA, Long Noncoding - metabolism</topic><topic>RNA, Messenger - metabolism</topic><topic>RNA, Small Interfering - metabolism</topic><topic>STAT3 Transcription Factor - genetics</topic><topic>STAT3 Transcription Factor - metabolism</topic><topic>TGF-β1</topic><topic>Transcriptome - drug effects</topic><topic>Transforming Growth Factor beta1 - pharmacology</topic><topic>Tumorigenesis</topic><topic>Up-Regulation - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hu, Wentao</creatorcontrib><creatorcontrib>Pei, Weiwei</creatorcontrib><creatorcontrib>Zhu, Lin</creatorcontrib><creatorcontrib>Nie, Jing</creatorcontrib><creatorcontrib>Pei, Hailong</creatorcontrib><creatorcontrib>Zhang, Jian</creatorcontrib><creatorcontrib>Li, Bingyan</creatorcontrib><creatorcontrib>Hei, Tom K.</creatorcontrib><creatorcontrib>Zhou, Guangming</creatorcontrib><collection>Karger Open Access</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>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>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><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Cellular physiology and biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hu, Wentao</au><au>Pei, Weiwei</au><au>Zhu, Lin</au><au>Nie, Jing</au><au>Pei, Hailong</au><au>Zhang, Jian</au><au>Li, Bingyan</au><au>Hei, Tom K.</au><au>Zhou, Guangming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Microarray Profiling of TGF-β1-Induced Long Non-Coding RNA Expression Patterns in Human Lung Bronchial Epithelial BEAS-2B Cells</atitle><jtitle>Cellular physiology and biochemistry</jtitle><addtitle>Cell Physiol Biochem</addtitle><date>2018-11-01</date><risdate>2018</risdate><volume>50</volume><issue>6</issue><spage>2071</spage><epage>2085</epage><pages>2071-2085</pages><issn>1015-8987</issn><eissn>1421-9778</eissn><abstract>Background/Aims: TGF-β1 mediated radiation-induced bystander effects (RIBE) have been linked with malignant transformation and tumorigenesis. However, the underlying mechanisms are not fully understood. Methods: To reveal new molecules of regulatory functions in this process, lncRNA microarray was performed to profile both lncRNA and mRNA expression patterns in human lung bronchial epithelial BEAS-2B cells treated with TGF-β1 at a concentration measured in the medium conditioned by directly irradiated BEAS-2B cells. The potential functions of the differentially expressed lncRNAs were predicted by GO and KEGG pathway analyses of their co-expressed mRNAs. Cis- and trans-regulation of the lncRNAs were analyzed and the interaction networks were constructed using Cytoscape. qRT-PCR was conducted to validate the results of microarray profiling. CCK-8 assay was employed for functional validation of 3 identified lncRNAs. Results: 224 lncRNAs were found to be dysregulated, among which 6 lncRNAs were chosen for expression validation by qRT-PCR assay. Pathway analyses showed that differentially expressed lncRNAs are highly correlated with cell proliferation, transformation, migration, etc. Trans-regulation analyses showed that the differentially expressed lncRNAs most likely participate in the pathways regulated by four transcriptional factors, FOS, STAT3, RAD21 and E2F1, which have been identified to be involved in the modulation of oncogenic transformation, cell cycle progression, genomic instability, etc. lnc-THEMIS-2 and lnc-ITGB6-4, predicted to be regulated by STAT3 and E2F1 respectively, were found to rescue the decrease of cell viability induced by TGF-β1 treatment. Conclusion: Our findings suggest that the differentially expressed lncRNAs induced by TGF-β1 play crucial roles in the oncogenic transformation and tumorigenesis, which provide a better understanding of the underlying mechanisms related to tumorigensis induced by LD/LDR radiations.</abstract><cop>Basel, Switzerland</cop><pub>S. Karger AG</pub><pmid>30423581</pmid><doi>10.1159/000495052</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | BEAS-2B Bronchi - cytology Cancer therapies Cell Line Cytokines Down-Regulation - drug effects Epithelial Cells - cytology Epithelial Cells - drug effects Epithelial Cells - metabolism Epithelial-Mesenchymal Transition - drug effects Fibronectins - metabolism Gene expression Gene Expression Profiling Gene Regulatory Networks - genetics Genomes Growth factors Humans Long non-coding RNA Microarray Original Paper Proto-Oncogene Proteins c-fos - genetics Proto-Oncogene Proteins c-fos - metabolism Radiation therapy RNA Interference RNA, Long Noncoding - antagonists & inhibitors RNA, Long Noncoding - genetics RNA, Long Noncoding - metabolism RNA, Messenger - metabolism RNA, Small Interfering - metabolism STAT3 Transcription Factor - genetics STAT3 Transcription Factor - metabolism TGF-β1 Transcriptome - drug effects Transforming Growth Factor beta1 - pharmacology Tumorigenesis Up-Regulation - drug effects |
| title | Microarray Profiling of TGF-β1-Induced Long Non-Coding RNA Expression Patterns in Human Lung Bronchial Epithelial BEAS-2B Cells |
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