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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Bibliographic Details
Published in:Cellular and molecular life sciences : CMLS 2018-06, Vol.75 (12), p.2241-2256
Main Authors: 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
Format: Article
Language:English
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
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Description
Summary: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.
ISSN:1420-682X
1420-9071
DOI:10.1007/s00018-017-2731-6