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Identification of differentially expressed long noncoding RNAs in bladder cancer

Item Type:Article
Title:Identification of differentially expressed long noncoding RNAs in bladder cancer
Creators Name:Peter, S. and Borkowska, E. and Drayton, R.M. and Rakhit, C.P. and Noon, A.P. and Chen, W. and Catto, J.W.F.
Abstract:Purpose: Loss of epigenetic gene regulation through altered long non-coding RNA (lncRNA) expression appears important in human cancer. LncRNAs have diagnostic and therapeutic potential, and offer insights into the biology disease, but little is known of their expression in urothelial cancer (UC). Here we identify differentially expressed lncRNAs with potential regulatory functions in UC. Experimental Design: The expression of 17,112 lncRNAs and 22,074 mRNAs was determined using microarrays in 83 normal and malignant urothelial (discovery) samples and selected RNAs with qPCR in 138 samples for validation. Significantly differentially expressed RNAs were identified and stratified according to tumour phenotype. siRNA knock-down, functional assays and whole genome transcriptomic profiling were used to identify potential roles of selected lncRNAs. Results: We observed upregulation of many lncRNAs in UC that was distinct to corresponding, more balanced changes for mRNAs. In general, lncRNA expression reflected disease phenotype. We identified 32 lncRNAs with potential roles in disease progression. Focusing upon a promising candidate, we implicate upregulation of AB074278 in apoptosis avoidance and the maintenance of a pro-proliferative state in cancer through a potential interaction with EMP1, a tumour suppressor and a negative regulator of cell proliferation. Conclusions: We report differentially expression profiles for numerous lncRNA in UC. We identify phenotype-specific expression and a potential mechanistic target to explain this observation. Further studies are required to validate lncRNAs as prognostic biomarkers in this disease.
Keywords:Long Non-Coding RNA, Transcription Profile, Bladder Cancer, Epigenetic Regulation
Source:Clinical Cancer Research
ISSN:1078-0432
Publisher:American Association for Cancer Research (U.S.A.)
Volume:20
Number:20
Page Range:5311-5321
Date:15 October 2014
Official Publication:https://doi.org/10.1158/1078-0432.CCR-14-0706
PubMed:View item in PubMed

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