Long noncoding RNA CRNDE stabilized by hnRNPUL2 accelerates cell proliferation and migration in colorectal carcinoma via activating Ras/MAPK signaling pathways

Recent studies have furthered our understanding of the function of long noncoding RNAs (lncRNAs) in numerous biological processes, including cancer. This study investigated the expression of a novel lncRNA, colorectal neoplasia differentially expressed ( CRNDE ), in colorectal carcinoma (CRC) tissue...

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Veröffentlicht in:Cell death & disease 2017-06, Vol.8 (6), p.e2862-e2862
Hauptverfasser: Jiang, Huijuan, Wang, Yiqing, Ai, Meiling, Wang, Haowei, Duan, Zhijiao, Wang, Huanan, Zhao, Li, Yu, Jiang, Ding, Yanqing, Wang, Shuang
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container_issue 6
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container_title Cell death & disease
container_volume 8
creator Jiang, Huijuan
Wang, Yiqing
Ai, Meiling
Wang, Haowei
Duan, Zhijiao
Wang, Huanan
Zhao, Li
Yu, Jiang
Ding, Yanqing
Wang, Shuang
description Recent studies have furthered our understanding of the function of long noncoding RNAs (lncRNAs) in numerous biological processes, including cancer. This study investigated the expression of a novel lncRNA, colorectal neoplasia differentially expressed ( CRNDE ), in colorectal carcinoma (CRC) tissues and cells by real-time RT-PCR and in situ hybridization, and its biological function using a series of in vitro and in vivo experiments to determine its potential as a prognostic marker and therapeutic target. CRNDE was found to be upregulated in primary CRC tissues and cells ( P
doi_str_mv 10.1038/cddis.2017.258
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This study investigated the expression of a novel lncRNA, colorectal neoplasia differentially expressed ( CRNDE ), in colorectal carcinoma (CRC) tissues and cells by real-time RT-PCR and in situ hybridization, and its biological function using a series of in vitro and in vivo experiments to determine its potential as a prognostic marker and therapeutic target. CRNDE was found to be upregulated in primary CRC tissues and cells ( P &lt;0.05), and the upregulation of CRNDE expression is a powerful predictor of advanced TNM stage ( P &lt;0.05) and poor prognosis for CRC patients ( P =0.002). The promoting effects of CRNDE on the cell proliferation, cell cycling and metastasis of CRC cells were confirmed both in vitro and in vivo by gain-of-function and loss-of-function experiments. Mechanistically, it was demonstrated that CRNDE could form a functional complex with heterogeneous nuclear ribonucleoprotein U-like 2 protein (hnRNPUL2) and direct the transport of hnRNPUL2 between the nucleus and cytoplasm. hnRNPUL2 that was accumulated in the cytoplasm could interact with CRNDE both physically and functionally, increasing the stability of CRNDE RNA. Moreover, gene expression profile data showed that CRNDE depletion in cells downregulated a series of genes involved in the Ras/mitogen-activated protein kinase signaling pathways. Collectively, these findings provide novel insights into the function and mechanism of lncRNA CRNDE in the pathogenesis of CRC and highlight its potential as a therapeutic target for CRC intervention.</description><identifier>ISSN: 2041-4889</identifier><identifier>EISSN: 2041-4889</identifier><identifier>DOI: 10.1038/cddis.2017.258</identifier><identifier>PMID: 28594403</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/89 ; 38/1 ; 631/337/384/2568 ; 631/80/86 ; 692/699/67/1504/1885 ; 692/699/67/322 ; 82/51 ; 82/80 ; Animals ; Antibodies ; Biochemistry ; Biomedical and Life Sciences ; Cell Biology ; Cell Culture ; Cell growth ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - metabolism ; Colorectal Neoplasms - pathology ; Cytoplasm ; Extracellular Signal-Regulated MAP Kinases - genetics ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Female ; Gene expression ; Heterogeneous-Nuclear Ribonucleoproteins - genetics ; Heterogeneous-Nuclear Ribonucleoproteins - metabolism ; Humans ; Immunology ; Kinases ; Life Sciences ; Male ; MAP kinase ; MAP Kinase Signaling System ; Metastases ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Original ; original-article ; Polymerase chain reaction ; Protein kinase ; Proto-Oncogene Proteins p21(ras) - genetics ; Proto-Oncogene Proteins p21(ras) - metabolism ; Ras protein ; Ribonucleic acid ; RNA ; RNA, Long Noncoding - genetics ; RNA, Long Noncoding - metabolism ; RNA, Neoplasm - genetics ; RNA, Neoplasm - metabolism ; Signal transduction</subject><ispartof>Cell death &amp; disease, 2017-06, Vol.8 (6), p.e2862-e2862</ispartof><rights>The Author(s) 2017</rights><rights>Copyright Nature Publishing Group Jun 2017</rights><rights>Copyright © 2017 The Author(s) 2017 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c524t-4e042e57cf1378e7acbebfc9310ea6c3ab0c5f639c60b1af7d86d5f08955502d3</citedby><cites>FETCH-LOGICAL-c524t-4e042e57cf1378e7acbebfc9310ea6c3ab0c5f639c60b1af7d86d5f08955502d3</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/PMC5520914/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520914/$$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/28594403$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jiang, Huijuan</creatorcontrib><creatorcontrib>Wang, Yiqing</creatorcontrib><creatorcontrib>Ai, Meiling</creatorcontrib><creatorcontrib>Wang, Haowei</creatorcontrib><creatorcontrib>Duan, Zhijiao</creatorcontrib><creatorcontrib>Wang, Huanan</creatorcontrib><creatorcontrib>Zhao, Li</creatorcontrib><creatorcontrib>Yu, Jiang</creatorcontrib><creatorcontrib>Ding, Yanqing</creatorcontrib><creatorcontrib>Wang, Shuang</creatorcontrib><title>Long noncoding RNA CRNDE stabilized by hnRNPUL2 accelerates cell proliferation and migration in colorectal carcinoma via activating Ras/MAPK signaling pathways</title><title>Cell death &amp; disease</title><addtitle>Cell Death Dis</addtitle><addtitle>Cell Death Dis</addtitle><description>Recent studies have furthered our understanding of the function of long noncoding RNAs (lncRNAs) in numerous biological processes, including cancer. This study investigated the expression of a novel lncRNA, colorectal neoplasia differentially expressed ( CRNDE ), in colorectal carcinoma (CRC) tissues and cells by real-time RT-PCR and in situ hybridization, and its biological function using a series of in vitro and in vivo experiments to determine its potential as a prognostic marker and therapeutic target. CRNDE was found to be upregulated in primary CRC tissues and cells ( P &lt;0.05), and the upregulation of CRNDE expression is a powerful predictor of advanced TNM stage ( P &lt;0.05) and poor prognosis for CRC patients ( P =0.002). The promoting effects of CRNDE on the cell proliferation, cell cycling and metastasis of CRC cells were confirmed both in vitro and in vivo by gain-of-function and loss-of-function experiments. Mechanistically, it was demonstrated that CRNDE could form a functional complex with heterogeneous nuclear ribonucleoprotein U-like 2 protein (hnRNPUL2) and direct the transport of hnRNPUL2 between the nucleus and cytoplasm. hnRNPUL2 that was accumulated in the cytoplasm could interact with CRNDE both physically and functionally, increasing the stability of CRNDE RNA. Moreover, gene expression profile data showed that CRNDE depletion in cells downregulated a series of genes involved in the Ras/mitogen-activated protein kinase signaling pathways. 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disease</jtitle><stitle>Cell Death Dis</stitle><addtitle>Cell Death Dis</addtitle><date>2017-06-08</date><risdate>2017</risdate><volume>8</volume><issue>6</issue><spage>e2862</spage><epage>e2862</epage><pages>e2862-e2862</pages><issn>2041-4889</issn><eissn>2041-4889</eissn><abstract>Recent studies have furthered our understanding of the function of long noncoding RNAs (lncRNAs) in numerous biological processes, including cancer. This study investigated the expression of a novel lncRNA, colorectal neoplasia differentially expressed ( CRNDE ), in colorectal carcinoma (CRC) tissues and cells by real-time RT-PCR and in situ hybridization, and its biological function using a series of in vitro and in vivo experiments to determine its potential as a prognostic marker and therapeutic target. CRNDE was found to be upregulated in primary CRC tissues and cells ( P &lt;0.05), and the upregulation of CRNDE expression is a powerful predictor of advanced TNM stage ( P &lt;0.05) and poor prognosis for CRC patients ( P =0.002). The promoting effects of CRNDE on the cell proliferation, cell cycling and metastasis of CRC cells were confirmed both in vitro and in vivo by gain-of-function and loss-of-function experiments. Mechanistically, it was demonstrated that CRNDE could form a functional complex with heterogeneous nuclear ribonucleoprotein U-like 2 protein (hnRNPUL2) and direct the transport of hnRNPUL2 between the nucleus and cytoplasm. hnRNPUL2 that was accumulated in the cytoplasm could interact with CRNDE both physically and functionally, increasing the stability of CRNDE RNA. Moreover, gene expression profile data showed that CRNDE depletion in cells downregulated a series of genes involved in the Ras/mitogen-activated protein kinase signaling pathways. Collectively, these findings provide novel insights into the function and mechanism of lncRNA CRNDE in the pathogenesis of CRC and highlight its potential as a therapeutic target for CRC intervention.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>28594403</pmid><doi>10.1038/cddis.2017.258</doi><oa>free_for_read</oa></addata></record>
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subjects 13/89
38/1
631/337/384/2568
631/80/86
692/699/67/1504/1885
692/699/67/322
82/51
82/80
Animals
Antibodies
Biochemistry
Biomedical and Life Sciences
Cell Biology
Cell Culture
Cell growth
Cell Line, Tumor
Cell Movement
Cell Proliferation
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - genetics
Colorectal Neoplasms - metabolism
Colorectal Neoplasms - pathology
Cytoplasm
Extracellular Signal-Regulated MAP Kinases - genetics
Extracellular Signal-Regulated MAP Kinases - metabolism
Female
Gene expression
Heterogeneous-Nuclear Ribonucleoproteins - genetics
Heterogeneous-Nuclear Ribonucleoproteins - metabolism
Humans
Immunology
Kinases
Life Sciences
Male
MAP kinase
MAP Kinase Signaling System
Metastases
Mice
Mice, Inbred BALB C
Mice, Nude
Original
original-article
Polymerase chain reaction
Protein kinase
Proto-Oncogene Proteins p21(ras) - genetics
Proto-Oncogene Proteins p21(ras) - metabolism
Ras protein
Ribonucleic acid
RNA
RNA, Long Noncoding - genetics
RNA, Long Noncoding - metabolism
RNA, Neoplasm - genetics
RNA, Neoplasm - metabolism
Signal transduction
title Long noncoding RNA CRNDE stabilized by hnRNPUL2 accelerates cell proliferation and migration in colorectal carcinoma via activating Ras/MAPK signaling pathways
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