Long noncoding RNA EGFR-AS1 promotes cell growth and metastasis via affecting HuR mediated mRNA stability of EGFR in renal cancer
Long noncoding RNAs (lncRNAs) are implicated in renal cell carcinoma (RCC), but remain largely unclear. Using publicly available transcriptome sequencing data from renal cancer ( n = 703) and integrating bioinformatics analyses, we screened and identified a valuable lncRNA, EGFR-AS1. In our validat...
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| description | Long noncoding RNAs (lncRNAs) are implicated in renal cell carcinoma (RCC), but remain largely unclear. Using publicly available transcriptome sequencing data from renal cancer (
n
= 703) and integrating bioinformatics analyses, we screened and identified a valuable lncRNA, EGFR-AS1. In our validation cohort (
n
= 204), EGFR-AS1 was significantly upregulated in RCC tissues (
P
<
0.001). Gain-of-function and loss-of-function studies showed that EGFR-AS1 promoted cell proliferation and invasion in vitro and in vivo. Based on previous studies and sequence complementarity of EGFR with EGFR-AS1, we demonstrated that EGFR-AS1 directly bound to EGFR mRNA and inhibited its degradation. Furthermore, RNA pull-down and mass spectrometry analyses showed that EGFR-AS1 interacted with HuR, which was responsible for the mRNA stability of EGFR. Multivariate analysis suggested that higher EGFR-AS1 expression predicted a poor prognosis in RCC patients (high vs low:
P
= 0.018, HR = 2.204, 95% CI: 1.145–4.241). In conclusion, EGFR-AS1 enhances the malignant phenotype of RCC cells by enhancing HuR-mediated mRNA stability of EGFR. Our data also provide biological rationales for EGFR-AS1 as a prognostic biomarker and a potential therapeutic target for RCC. |
| doi_str_mv | 10.1038/s41419-019-1331-9 |
| format | Article |
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n
= 703) and integrating bioinformatics analyses, we screened and identified a valuable lncRNA, EGFR-AS1. In our validation cohort (
n
= 204), EGFR-AS1 was significantly upregulated in RCC tissues (
P
<
0.001). Gain-of-function and loss-of-function studies showed that EGFR-AS1 promoted cell proliferation and invasion in vitro and in vivo. Based on previous studies and sequence complementarity of EGFR with EGFR-AS1, we demonstrated that EGFR-AS1 directly bound to EGFR mRNA and inhibited its degradation. Furthermore, RNA pull-down and mass spectrometry analyses showed that EGFR-AS1 interacted with HuR, which was responsible for the mRNA stability of EGFR. Multivariate analysis suggested that higher EGFR-AS1 expression predicted a poor prognosis in RCC patients (high vs low:
P
= 0.018, HR = 2.204, 95% CI: 1.145–4.241). In conclusion, EGFR-AS1 enhances the malignant phenotype of RCC cells by enhancing HuR-mediated mRNA stability of EGFR. Our data also provide biological rationales for EGFR-AS1 as a prognostic biomarker and a potential therapeutic target for RCC.</description><identifier>ISSN: 2041-4889</identifier><identifier>EISSN: 2041-4889</identifier><identifier>DOI: 10.1038/s41419-019-1331-9</identifier><identifier>PMID: 30770799</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>38/32 ; 631/67/1059/153 ; 631/67/589/1588/1351 ; 64/60 ; 82/80 ; Antibodies ; Biochemistry ; Bioinformatics ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Biomedical and Life Sciences ; Carcinoma, Renal Cell - metabolism ; Carcinoma, Renal Cell - mortality ; Carcinoma, Renal Cell - pathology ; Cell Biology ; Cell Culture ; Cell growth ; Cell Line, Tumor ; Cell proliferation ; Cell Proliferation - genetics ; Complementarity ; ELAV-Like Protein 1 - metabolism ; Epidermal growth factor receptors ; ErbB Receptors - genetics ; ErbB Receptors - metabolism ; Female ; Follow-Up Studies ; Gene expression ; Gene Knockdown Techniques ; Humans ; HuR protein ; Immunology ; Kidney cancer ; Kidney Neoplasms - metabolism ; Kidney Neoplasms - mortality ; Kidney Neoplasms - pathology ; Life Sciences ; Male ; Mass spectroscopy ; Metastases ; Middle Aged ; mRNA stability ; Multivariate analysis ; Neoplasm Invasiveness - genetics ; Neoplasm Metastasis - genetics ; Phenotypes ; Prognosis ; Renal cell carcinoma ; RNA Interference ; RNA Stability - genetics ; RNA, Long Noncoding - genetics ; RNA, Messenger - metabolism ; Survival Rate ; Therapeutic applications ; Transfection ; Up-Regulation</subject><ispartof>Cell death & disease, 2019-02, Vol.10 (3), p.154-154, Article 154</ispartof><rights>The Author(s) 2019</rights><rights>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-c470t-7ad9c47e035fb577ffd379efbd3cb2760e043a696e2548e6f3fdeff57ff01edb3</citedby><cites>FETCH-LOGICAL-c470t-7ad9c47e035fb577ffd379efbd3cb2760e043a696e2548e6f3fdeff57ff01edb3</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/PMC6377662/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377662/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27922,27923,41118,42187,51574,53789,53791</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30770799$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Anbang</creatorcontrib><creatorcontrib>Bao, Yi</creatorcontrib><creatorcontrib>Wu, Zhenjie</creatorcontrib><creatorcontrib>Zhao, Tangliang</creatorcontrib><creatorcontrib>Wang, Dong</creatorcontrib><creatorcontrib>Shi, Jiazi</creatorcontrib><creatorcontrib>Liu, Bing</creatorcontrib><creatorcontrib>Sun, Shuhan</creatorcontrib><creatorcontrib>Yang, Fu</creatorcontrib><creatorcontrib>Wang, Linhui</creatorcontrib><creatorcontrib>Qu, Le</creatorcontrib><title>Long noncoding RNA EGFR-AS1 promotes cell growth and metastasis via affecting HuR mediated mRNA stability of EGFR in renal cancer</title><title>Cell death & disease</title><addtitle>Cell Death Dis</addtitle><addtitle>Cell Death Dis</addtitle><description>Long noncoding RNAs (lncRNAs) are implicated in renal cell carcinoma (RCC), but remain largely unclear. Using publicly available transcriptome sequencing data from renal cancer (
n
= 703) and integrating bioinformatics analyses, we screened and identified a valuable lncRNA, EGFR-AS1. In our validation cohort (
n
= 204), EGFR-AS1 was significantly upregulated in RCC tissues (
P
<
0.001). Gain-of-function and loss-of-function studies showed that EGFR-AS1 promoted cell proliferation and invasion in vitro and in vivo. Based on previous studies and sequence complementarity of EGFR with EGFR-AS1, we demonstrated that EGFR-AS1 directly bound to EGFR mRNA and inhibited its degradation. Furthermore, RNA pull-down and mass spectrometry analyses showed that EGFR-AS1 interacted with HuR, which was responsible for the mRNA stability of EGFR. Multivariate analysis suggested that higher EGFR-AS1 expression predicted a poor prognosis in RCC patients (high vs low:
P
= 0.018, HR = 2.204, 95% CI: 1.145–4.241). In conclusion, EGFR-AS1 enhances the malignant phenotype of RCC cells by enhancing HuR-mediated mRNA stability of EGFR. Our data also provide biological rationales for EGFR-AS1 as a prognostic biomarker and a potential therapeutic target for RCC.</description><subject>38/32</subject><subject>631/67/1059/153</subject><subject>631/67/589/1588/1351</subject><subject>64/60</subject><subject>82/80</subject><subject>Antibodies</subject><subject>Biochemistry</subject><subject>Bioinformatics</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Biomedical and Life Sciences</subject><subject>Carcinoma, Renal Cell - metabolism</subject><subject>Carcinoma, Renal Cell - mortality</subject><subject>Carcinoma, Renal Cell - pathology</subject><subject>Cell Biology</subject><subject>Cell Culture</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - genetics</subject><subject>Complementarity</subject><subject>ELAV-Like Protein 1 - metabolism</subject><subject>Epidermal growth factor receptors</subject><subject>ErbB Receptors - genetics</subject><subject>ErbB Receptors - metabolism</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Gene expression</subject><subject>Gene Knockdown Techniques</subject><subject>Humans</subject><subject>HuR protein</subject><subject>Immunology</subject><subject>Kidney cancer</subject><subject>Kidney Neoplasms - metabolism</subject><subject>Kidney Neoplasms - mortality</subject><subject>Kidney Neoplasms - pathology</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Mass spectroscopy</subject><subject>Metastases</subject><subject>Middle Aged</subject><subject>mRNA stability</subject><subject>Multivariate analysis</subject><subject>Neoplasm Invasiveness - genetics</subject><subject>Neoplasm Metastasis - genetics</subject><subject>Phenotypes</subject><subject>Prognosis</subject><subject>Renal cell carcinoma</subject><subject>RNA Interference</subject><subject>RNA Stability - genetics</subject><subject>RNA, Long Noncoding - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Survival Rate</subject><subject>Therapeutic applications</subject><subject>Transfection</subject><subject>Up-Regulation</subject><issn>2041-4889</issn><issn>2041-4889</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kU1r3DAQhkVpacI2P6CXIuilF7eSZVvWpbCEfBSWFDbpWcjyaKPglbaSnZBj_3nH2TRNChUSGphnXs3oJeQ9Z585E-2XXPGKq4Lh4ULwQr0ihyWreFG1rXr9LD4gRznfMFxCsLJu3pIDwaRkUqlD8msVw4aGGGzsPUbriyU9OTtdF8tLTncpbuMImVoYBrpJ8W68pib0dAujybh9prfeUOMc2HEuP5_WmOy9GQGpWQyxzg9-vKfRPShTH2iCYAZqTbCQ3pE3zgwZjh7vBflxenJ1fF6svp99O16uCltJNhbS9AojYKJ2XS2lc72QClzXC9uVsmHAKmEa1UBZVy00TrgenKsRZBz6TizI173ubuqwRQthTGbQu-S3Jt3raLx-mQn-Wm_irW6ElE1TosCnR4EUf06QR731ef4ZEyBOWZe8RUtKxiSiH_9Bb-KUcOYHikspKzRjQfiesinmnMA9NcOZnj3We481eqxnj7XCmg_Pp3iq-OMoAuUeyJgKG0h_n_6_6m_fwrJ7</recordid><startdate>20190215</startdate><enddate>20190215</enddate><creator>Wang, Anbang</creator><creator>Bao, Yi</creator><creator>Wu, Zhenjie</creator><creator>Zhao, Tangliang</creator><creator>Wang, Dong</creator><creator>Shi, Jiazi</creator><creator>Liu, Bing</creator><creator>Sun, Shuhan</creator><creator>Yang, Fu</creator><creator>Wang, Linhui</creator><creator>Qu, Le</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20190215</creationdate><title>Long noncoding RNA EGFR-AS1 promotes cell growth and metastasis via affecting HuR mediated mRNA stability of EGFR in renal cancer</title><author>Wang, Anbang ; Bao, Yi ; Wu, Zhenjie ; Zhao, Tangliang ; Wang, Dong ; Shi, Jiazi ; Liu, Bing ; Sun, Shuhan ; Yang, Fu ; Wang, Linhui ; Qu, Le</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-7ad9c47e035fb577ffd379efbd3cb2760e043a696e2548e6f3fdeff57ff01edb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>38/32</topic><topic>631/67/1059/153</topic><topic>631/67/589/1588/1351</topic><topic>64/60</topic><topic>82/80</topic><topic>Antibodies</topic><topic>Biochemistry</topic><topic>Bioinformatics</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Biomedical and Life Sciences</topic><topic>Carcinoma, Renal Cell - metabolism</topic><topic>Carcinoma, Renal Cell - mortality</topic><topic>Carcinoma, Renal Cell - pathology</topic><topic>Cell Biology</topic><topic>Cell Culture</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell proliferation</topic><topic>Cell Proliferation - genetics</topic><topic>Complementarity</topic><topic>ELAV-Like Protein 1 - metabolism</topic><topic>Epidermal growth factor receptors</topic><topic>ErbB Receptors - genetics</topic><topic>ErbB Receptors - metabolism</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Gene expression</topic><topic>Gene Knockdown Techniques</topic><topic>Humans</topic><topic>HuR protein</topic><topic>Immunology</topic><topic>Kidney cancer</topic><topic>Kidney Neoplasms - metabolism</topic><topic>Kidney Neoplasms - mortality</topic><topic>Kidney Neoplasms - pathology</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Mass spectroscopy</topic><topic>Metastases</topic><topic>Middle Aged</topic><topic>mRNA stability</topic><topic>Multivariate analysis</topic><topic>Neoplasm Invasiveness - genetics</topic><topic>Neoplasm Metastasis - genetics</topic><topic>Phenotypes</topic><topic>Prognosis</topic><topic>Renal cell carcinoma</topic><topic>RNA Interference</topic><topic>RNA Stability - genetics</topic><topic>RNA, Long Noncoding - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Survival Rate</topic><topic>Therapeutic applications</topic><topic>Transfection</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Anbang</creatorcontrib><creatorcontrib>Bao, Yi</creatorcontrib><creatorcontrib>Wu, Zhenjie</creatorcontrib><creatorcontrib>Zhao, Tangliang</creatorcontrib><creatorcontrib>Wang, Dong</creatorcontrib><creatorcontrib>Shi, Jiazi</creatorcontrib><creatorcontrib>Liu, Bing</creatorcontrib><creatorcontrib>Sun, Shuhan</creatorcontrib><creatorcontrib>Yang, Fu</creatorcontrib><creatorcontrib>Wang, Linhui</creatorcontrib><creatorcontrib>Qu, Le</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>MEDLINE - Academic</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>Wang, Anbang</au><au>Bao, Yi</au><au>Wu, Zhenjie</au><au>Zhao, Tangliang</au><au>Wang, Dong</au><au>Shi, Jiazi</au><au>Liu, Bing</au><au>Sun, Shuhan</au><au>Yang, Fu</au><au>Wang, Linhui</au><au>Qu, Le</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Long noncoding RNA EGFR-AS1 promotes cell growth and metastasis via affecting HuR mediated mRNA stability of EGFR in renal cancer</atitle><jtitle>Cell death & disease</jtitle><stitle>Cell Death Dis</stitle><addtitle>Cell Death Dis</addtitle><date>2019-02-15</date><risdate>2019</risdate><volume>10</volume><issue>3</issue><spage>154</spage><epage>154</epage><pages>154-154</pages><artnum>154</artnum><issn>2041-4889</issn><eissn>2041-4889</eissn><abstract>Long noncoding RNAs (lncRNAs) are implicated in renal cell carcinoma (RCC), but remain largely unclear. Using publicly available transcriptome sequencing data from renal cancer (
n
= 703) and integrating bioinformatics analyses, we screened and identified a valuable lncRNA, EGFR-AS1. In our validation cohort (
n
= 204), EGFR-AS1 was significantly upregulated in RCC tissues (
P
<
0.001). Gain-of-function and loss-of-function studies showed that EGFR-AS1 promoted cell proliferation and invasion in vitro and in vivo. Based on previous studies and sequence complementarity of EGFR with EGFR-AS1, we demonstrated that EGFR-AS1 directly bound to EGFR mRNA and inhibited its degradation. Furthermore, RNA pull-down and mass spectrometry analyses showed that EGFR-AS1 interacted with HuR, which was responsible for the mRNA stability of EGFR. Multivariate analysis suggested that higher EGFR-AS1 expression predicted a poor prognosis in RCC patients (high vs low:
P
= 0.018, HR = 2.204, 95% CI: 1.145–4.241). In conclusion, EGFR-AS1 enhances the malignant phenotype of RCC cells by enhancing HuR-mediated mRNA stability of EGFR. Our data also provide biological rationales for EGFR-AS1 as a prognostic biomarker and a potential therapeutic target for RCC.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30770799</pmid><doi>10.1038/s41419-019-1331-9</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 38/32 631/67/1059/153 631/67/589/1588/1351 64/60 82/80 Antibodies Biochemistry Bioinformatics Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Biomedical and Life Sciences Carcinoma, Renal Cell - metabolism Carcinoma, Renal Cell - mortality Carcinoma, Renal Cell - pathology Cell Biology Cell Culture Cell growth Cell Line, Tumor Cell proliferation Cell Proliferation - genetics Complementarity ELAV-Like Protein 1 - metabolism Epidermal growth factor receptors ErbB Receptors - genetics ErbB Receptors - metabolism Female Follow-Up Studies Gene expression Gene Knockdown Techniques Humans HuR protein Immunology Kidney cancer Kidney Neoplasms - metabolism Kidney Neoplasms - mortality Kidney Neoplasms - pathology Life Sciences Male Mass spectroscopy Metastases Middle Aged mRNA stability Multivariate analysis Neoplasm Invasiveness - genetics Neoplasm Metastasis - genetics Phenotypes Prognosis Renal cell carcinoma RNA Interference RNA Stability - genetics RNA, Long Noncoding - genetics RNA, Messenger - metabolism Survival Rate Therapeutic applications Transfection Up-Regulation |
| title | Long noncoding RNA EGFR-AS1 promotes cell growth and metastasis via affecting HuR mediated mRNA stability of EGFR in renal cancer |
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