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Identification of a novel lncRNA induced by the nephrotoxin ochratoxin A and expressed in human renal tumor tissue
Long non-coding RNAs represent a fraction of the transcriptome that is being increasingly recognized. For most of them no function has been allocated so far. Here, we describe the nature and function of a novel non-protein-coding transcript, named WISP1-AS1, discovered in human renal proximal tubule...
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Published in: | Cellular and molecular life sciences : CMLS 2018-06, Vol.75 (12), p.2241-2256 |
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creator | Polovic, Mirjana Dittmar, Sandro Hennemeier, Isabell Humpf, Hans-Ulrich Seliger, Barbara Fornara, Paolo Theil, Gerit Azinovic, Patrick Nolze, Alexander Köhn, Marcel Schwerdt, Gerald Gekle, Michael |
description | Long non-coding RNAs represent a fraction of the transcriptome that is being increasingly recognized. For most of them no function has been allocated so far. Here, we describe the nature and function of a novel non-protein-coding transcript, named WISP1-AS1, discovered in human renal proximal tubule cells exposed to the carcinogenic nephrotoxin ochratoxin A. WISP1-AS1 overlaps parts of the fourth intron and fifth exon of the Wnt1-inducible signaling pathway protein 1 (WISP1) gene. The transcript is 2922 nucleotides long, transcribed in antisense direction and predominantly localized in the nucleus. WISP1-AS1 is expressed in all 20 samples of a human tissue RNA panel with the highest expression levels detected in uterus, kidney and adrenal gland. Its expression was confirmed in primary tissues of human kidneys. In addition, WISP1-AS1 is expressed at higher levels in renal cell carcinoma (RCC) cell lines compared to primary proximal tubule cells as well as in RCC lesions than in the adjacent healthy control tissue from the same patient. Using specific gapmer antisense oligonucleotides to prevent its upregulation, we show that WISP1-AS1 (1) does not influence the mRNA expression of WISP1, (2) affects transcriptional regulation by Egr-1 and E2F as revealed by RNA-sequencing, enrichment analysis and reporter assays, and (3) modulates the apoptosis-necrosis balance. In summary, WISP1-AS1 is a novel lncRNA with modulatory transcriptional function and the potential to alter the cellular phenotype in situations of stress or oncogenic transformation. However, its precise mode of action and impact on cellular functions require further investigations. |
doi_str_mv | 10.1007/s00018-017-2731-6 |
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For most of them no function has been allocated so far. Here, we describe the nature and function of a novel non-protein-coding transcript, named WISP1-AS1, discovered in human renal proximal tubule cells exposed to the carcinogenic nephrotoxin ochratoxin A. WISP1-AS1 overlaps parts of the fourth intron and fifth exon of the Wnt1-inducible signaling pathway protein 1 (WISP1) gene. The transcript is 2922 nucleotides long, transcribed in antisense direction and predominantly localized in the nucleus. WISP1-AS1 is expressed in all 20 samples of a human tissue RNA panel with the highest expression levels detected in uterus, kidney and adrenal gland. Its expression was confirmed in primary tissues of human kidneys. In addition, WISP1-AS1 is expressed at higher levels in renal cell carcinoma (RCC) cell lines compared to primary proximal tubule cells as well as in RCC lesions than in the adjacent healthy control tissue from the same patient. Using specific gapmer antisense oligonucleotides to prevent its upregulation, we show that WISP1-AS1 (1) does not influence the mRNA expression of WISP1, (2) affects transcriptional regulation by Egr-1 and E2F as revealed by RNA-sequencing, enrichment analysis and reporter assays, and (3) modulates the apoptosis-necrosis balance. In summary, WISP1-AS1 is a novel lncRNA with modulatory transcriptional function and the potential to alter the cellular phenotype in situations of stress or oncogenic transformation. However, its precise mode of action and impact on cellular functions require further investigations.</description><identifier>ISSN: 1420-682X</identifier><identifier>EISSN: 1420-9071</identifier><identifier>DOI: 10.1007/s00018-017-2731-6</identifier><identifier>PMID: 29282485</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Adrenal glands ; Antisense oligonucleotides ; Apoptosis ; Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; Carcinogenesis - chemically induced ; Carcinogenesis - genetics ; Carcinogenesis - pathology ; Carcinogens ; Carcinogens - toxicity ; CCN Intercellular Signaling Proteins - genetics ; Cell Biology ; Cell Death ; Cell Line, Tumor ; E2F protein ; EGR-1 protein ; Gene expression ; Gene Expression Regulation, Neoplastic - drug effects ; Gene regulation ; Gene sequencing ; Genes ; Genetic transformation ; Genomes ; HEK293 Cells ; Humans ; Kidney - drug effects ; Kidney - metabolism ; Kidney - pathology ; Kidney cancer ; Kidney Neoplasms - chemically induced ; Kidney Neoplasms - genetics ; Kidney Neoplasms - pathology ; Kidneys ; Lesions ; Life Sciences ; Mode of action ; Nuclei ; Nucleotides ; Ochratoxin A ; Ochratoxins - toxicity ; Oligonucleotides ; Original ; Original Article ; Proteins ; Proto-Oncogene Proteins - genetics ; Renal cell carcinoma ; Ribonucleic acid ; RNA ; RNA, Long Noncoding - genetics ; RNA, Messenger - genetics ; Signal transduction ; Signaling ; Tissues ; Transcription ; Tumor cell lines ; Uterus</subject><ispartof>Cellular and molecular life sciences : CMLS, 2018-06, Vol.75 (12), p.2241-2256</ispartof><rights>Springer International Publishing AG, part of Springer Nature 2017</rights><rights>Cellular and Molecular Life Sciences is a copyright of Springer, (2017). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c494t-e24457e548bee68de455697f2cf99f5bcef7406be85f2ca2e74fb12098958e483</citedby><cites>FETCH-LOGICAL-c494t-e24457e548bee68de455697f2cf99f5bcef7406be85f2ca2e74fb12098958e483</cites><orcidid>0000-0002-1581-8767</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/PMC11105410/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11105410/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,733,786,790,891,27957,27958,53827,53829</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29282485$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Polovic, Mirjana</creatorcontrib><creatorcontrib>Dittmar, Sandro</creatorcontrib><creatorcontrib>Hennemeier, Isabell</creatorcontrib><creatorcontrib>Humpf, Hans-Ulrich</creatorcontrib><creatorcontrib>Seliger, Barbara</creatorcontrib><creatorcontrib>Fornara, Paolo</creatorcontrib><creatorcontrib>Theil, Gerit</creatorcontrib><creatorcontrib>Azinovic, Patrick</creatorcontrib><creatorcontrib>Nolze, Alexander</creatorcontrib><creatorcontrib>Köhn, Marcel</creatorcontrib><creatorcontrib>Schwerdt, Gerald</creatorcontrib><creatorcontrib>Gekle, Michael</creatorcontrib><title>Identification of a novel lncRNA induced by the nephrotoxin ochratoxin A and expressed in human renal tumor tissue</title><title>Cellular and molecular life sciences : CMLS</title><addtitle>Cell. Mol. Life Sci</addtitle><addtitle>Cell Mol Life Sci</addtitle><description>Long non-coding RNAs represent a fraction of the transcriptome that is being increasingly recognized. For most of them no function has been allocated so far. Here, we describe the nature and function of a novel non-protein-coding transcript, named WISP1-AS1, discovered in human renal proximal tubule cells exposed to the carcinogenic nephrotoxin ochratoxin A. WISP1-AS1 overlaps parts of the fourth intron and fifth exon of the Wnt1-inducible signaling pathway protein 1 (WISP1) gene. The transcript is 2922 nucleotides long, transcribed in antisense direction and predominantly localized in the nucleus. WISP1-AS1 is expressed in all 20 samples of a human tissue RNA panel with the highest expression levels detected in uterus, kidney and adrenal gland. Its expression was confirmed in primary tissues of human kidneys. In addition, WISP1-AS1 is expressed at higher levels in renal cell carcinoma (RCC) cell lines compared to primary proximal tubule cells as well as in RCC lesions than in the adjacent healthy control tissue from the same patient. Using specific gapmer antisense oligonucleotides to prevent its upregulation, we show that WISP1-AS1 (1) does not influence the mRNA expression of WISP1, (2) affects transcriptional regulation by Egr-1 and E2F as revealed by RNA-sequencing, enrichment analysis and reporter assays, and (3) modulates the apoptosis-necrosis balance. In summary, WISP1-AS1 is a novel lncRNA with modulatory transcriptional function and the potential to alter the cellular phenotype in situations of stress or oncogenic transformation. However, its precise mode of action and impact on cellular functions require further investigations.</description><subject>Adrenal glands</subject><subject>Antisense oligonucleotides</subject><subject>Apoptosis</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Carcinogenesis - chemically induced</subject><subject>Carcinogenesis - genetics</subject><subject>Carcinogenesis - pathology</subject><subject>Carcinogens</subject><subject>Carcinogens - toxicity</subject><subject>CCN Intercellular Signaling Proteins - genetics</subject><subject>Cell Biology</subject><subject>Cell Death</subject><subject>Cell Line, Tumor</subject><subject>E2F protein</subject><subject>EGR-1 protein</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Gene regulation</subject><subject>Gene sequencing</subject><subject>Genes</subject><subject>Genetic transformation</subject><subject>Genomes</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Kidney - drug effects</subject><subject>Kidney - metabolism</subject><subject>Kidney - pathology</subject><subject>Kidney cancer</subject><subject>Kidney Neoplasms - chemically induced</subject><subject>Kidney Neoplasms - genetics</subject><subject>Kidney Neoplasms - pathology</subject><subject>Kidneys</subject><subject>Lesions</subject><subject>Life Sciences</subject><subject>Mode of action</subject><subject>Nuclei</subject><subject>Nucleotides</subject><subject>Ochratoxin A</subject><subject>Ochratoxins - toxicity</subject><subject>Oligonucleotides</subject><subject>Original</subject><subject>Original Article</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Renal cell carcinoma</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Long Noncoding - genetics</subject><subject>RNA, Messenger - genetics</subject><subject>Signal transduction</subject><subject>Signaling</subject><subject>Tissues</subject><subject>Transcription</subject><subject>Tumor cell lines</subject><subject>Uterus</subject><issn>1420-682X</issn><issn>1420-9071</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp1kU1r3DAQhkVJaT7aH9BLEOTsVFIkWzqFJSRtICRQEuhNyPJoreCVtpK97P77Kni7pIeeNMw8886MXoS-UnJJCWm-ZUIIlRWhTcWaK1rVH9AJ5YxUijT0aB_Xkv06Rqc5vxZYSFZ_QsdMMcm4FCco3XcQRu-8NaOPAUeHDQ5xAwMegv35uMA-dJOFDrc7PPaAA6z7FMe49QW2fTJzuMAmdBi26wQ5F7qk-mllAk4QzIDHaRUTHn3OE3xGH50ZMnzZv2fo5e72-eZH9fD0_f5m8VBZrvhYAeNcNCC4bAFq2QEXolaNY9Yp5URrwTWc1C1IUXKGQcNdSxlRUgkJXF6doetZdz21K-hsuTOZQa-TX5m009F4_W8l-F4v40ZTSonglBSFi71Cir8nyKN-jVMq92RNlSRSlL9lhaIzZVPMOYE7jKBEv_mkZ5908Um_-aTr0nP-frdDx19jCsBmIJdSWEJ6N_q_qn8AdjOgFA</recordid><startdate>20180601</startdate><enddate>20180601</enddate><creator>Polovic, Mirjana</creator><creator>Dittmar, 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of a novel lncRNA induced by the nephrotoxin ochratoxin A and expressed in human renal tumor tissue</title><author>Polovic, Mirjana ; Dittmar, Sandro ; Hennemeier, Isabell ; Humpf, Hans-Ulrich ; Seliger, Barbara ; Fornara, Paolo ; Theil, Gerit ; Azinovic, Patrick ; Nolze, Alexander ; Köhn, Marcel ; Schwerdt, Gerald ; Gekle, Michael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c494t-e24457e548bee68de455697f2cf99f5bcef7406be85f2ca2e74fb12098958e483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adrenal glands</topic><topic>Antisense oligonucleotides</topic><topic>Apoptosis</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Carcinogenesis - chemically induced</topic><topic>Carcinogenesis - genetics</topic><topic>Carcinogenesis - pathology</topic><topic>Carcinogens</topic><topic>Carcinogens - toxicity</topic><topic>CCN Intercellular Signaling Proteins - genetics</topic><topic>Cell Biology</topic><topic>Cell Death</topic><topic>Cell Line, Tumor</topic><topic>E2F protein</topic><topic>EGR-1 protein</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Gene regulation</topic><topic>Gene sequencing</topic><topic>Genes</topic><topic>Genetic transformation</topic><topic>Genomes</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Kidney - drug effects</topic><topic>Kidney - metabolism</topic><topic>Kidney - pathology</topic><topic>Kidney cancer</topic><topic>Kidney Neoplasms - chemically induced</topic><topic>Kidney Neoplasms - genetics</topic><topic>Kidney Neoplasms - pathology</topic><topic>Kidneys</topic><topic>Lesions</topic><topic>Life Sciences</topic><topic>Mode of action</topic><topic>Nuclei</topic><topic>Nucleotides</topic><topic>Ochratoxin A</topic><topic>Ochratoxins - toxicity</topic><topic>Oligonucleotides</topic><topic>Original</topic><topic>Original Article</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Renal cell carcinoma</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA, Long Noncoding - genetics</topic><topic>RNA, Messenger - genetics</topic><topic>Signal transduction</topic><topic>Signaling</topic><topic>Tissues</topic><topic>Transcription</topic><topic>Tumor cell lines</topic><topic>Uterus</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Polovic, Mirjana</creatorcontrib><creatorcontrib>Dittmar, Sandro</creatorcontrib><creatorcontrib>Hennemeier, Isabell</creatorcontrib><creatorcontrib>Humpf, Hans-Ulrich</creatorcontrib><creatorcontrib>Seliger, Barbara</creatorcontrib><creatorcontrib>Fornara, Paolo</creatorcontrib><creatorcontrib>Theil, Gerit</creatorcontrib><creatorcontrib>Azinovic, Patrick</creatorcontrib><creatorcontrib>Nolze, 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Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Polovic, Mirjana</au><au>Dittmar, Sandro</au><au>Hennemeier, Isabell</au><au>Humpf, Hans-Ulrich</au><au>Seliger, Barbara</au><au>Fornara, Paolo</au><au>Theil, Gerit</au><au>Azinovic, Patrick</au><au>Nolze, Alexander</au><au>Köhn, Marcel</au><au>Schwerdt, Gerald</au><au>Gekle, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of a novel lncRNA induced by the nephrotoxin ochratoxin A and expressed in human renal tumor tissue</atitle><jtitle>Cellular and molecular life sciences : CMLS</jtitle><stitle>Cell. Mol. Life Sci</stitle><addtitle>Cell Mol Life Sci</addtitle><date>2018-06-01</date><risdate>2018</risdate><volume>75</volume><issue>12</issue><spage>2241</spage><epage>2256</epage><pages>2241-2256</pages><issn>1420-682X</issn><eissn>1420-9071</eissn><abstract>Long non-coding RNAs represent a fraction of the transcriptome that is being increasingly recognized. For most of them no function has been allocated so far. Here, we describe the nature and function of a novel non-protein-coding transcript, named WISP1-AS1, discovered in human renal proximal tubule cells exposed to the carcinogenic nephrotoxin ochratoxin A. WISP1-AS1 overlaps parts of the fourth intron and fifth exon of the Wnt1-inducible signaling pathway protein 1 (WISP1) gene. The transcript is 2922 nucleotides long, transcribed in antisense direction and predominantly localized in the nucleus. WISP1-AS1 is expressed in all 20 samples of a human tissue RNA panel with the highest expression levels detected in uterus, kidney and adrenal gland. Its expression was confirmed in primary tissues of human kidneys. In addition, WISP1-AS1 is expressed at higher levels in renal cell carcinoma (RCC) cell lines compared to primary proximal tubule cells as well as in RCC lesions than in the adjacent healthy control tissue from the same patient. Using specific gapmer antisense oligonucleotides to prevent its upregulation, we show that WISP1-AS1 (1) does not influence the mRNA expression of WISP1, (2) affects transcriptional regulation by Egr-1 and E2F as revealed by RNA-sequencing, enrichment analysis and reporter assays, and (3) modulates the apoptosis-necrosis balance. In summary, WISP1-AS1 is a novel lncRNA with modulatory transcriptional function and the potential to alter the cellular phenotype in situations of stress or oncogenic transformation. However, its precise mode of action and impact on cellular functions require further investigations.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>29282485</pmid><doi>10.1007/s00018-017-2731-6</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-1581-8767</orcidid></addata></record> |
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subjects | Adrenal glands Antisense oligonucleotides Apoptosis Biochemistry Biomedical and Life Sciences Biomedicine Carcinogenesis - chemically induced Carcinogenesis - genetics Carcinogenesis - pathology Carcinogens Carcinogens - toxicity CCN Intercellular Signaling Proteins - genetics Cell Biology Cell Death Cell Line, Tumor E2F protein EGR-1 protein Gene expression Gene Expression Regulation, Neoplastic - drug effects Gene regulation Gene sequencing Genes Genetic transformation Genomes HEK293 Cells Humans Kidney - drug effects Kidney - metabolism Kidney - pathology Kidney cancer Kidney Neoplasms - chemically induced Kidney Neoplasms - genetics Kidney Neoplasms - pathology Kidneys Lesions Life Sciences Mode of action Nuclei Nucleotides Ochratoxin A Ochratoxins - toxicity Oligonucleotides Original Original Article Proteins Proto-Oncogene Proteins - genetics Renal cell carcinoma Ribonucleic acid RNA RNA, Long Noncoding - genetics RNA, Messenger - genetics Signal transduction Signaling Tissues Transcription Tumor cell lines Uterus |
title | Identification of a novel lncRNA induced by the nephrotoxin ochratoxin A and expressed in human renal tumor tissue |
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