Identification of long non-coding RNAs that stimulate cell survival in bladder cancer
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Aleksandra M. Dudek1, Sabrina J. Boer1, Nanda Boon1, J. Alfred Witjes1, Lambertus A.L.M. Kiemeney1,2, Gerald W. Verhaegh1
1Department of Urology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands
2Department for Health Evidence, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands
Gerald W. Verhaegh, email: Gerald.Verhaegh@radboudumc.nl
Keywords: long non-coding RNA, bladder cancer, MiTranscriptome, lncRNA, biomarker
Received: December 14, 2016 Accepted: March 08, 2017 Published: March 16, 2017
For many years, research on the biology underlying bladder cancer focused on protein-coding genes which cover only about 3% of the human genome. Recently, it was discovered that a large part of the human genome is actively transcribed as long non-coding RNAs (lncRNAs). LncRNAs are master regulators of gene expression and several lncRNAs were shown to play a role in bladder cancer development and progression. Here, we analyzed lncRNA expression in muscle-invasive bladder cancer (MIBC) using the MiTranscriptome database of cancer lncRNA expression profiles, and we studied their function in bladder cancer-derived tumor cells. Analysis of the MiTranscriptome lncRNA expression data revealed four MIBC subgroups, which partially overlapped with the four mRNA clusters identified by The Cancer Genome Atlas consortium. Up-regulation of three lncRNAs CAT266, CAT1297, and CAT1647 in bladder cancer, in comparison to normal urothelium, was confirmed in an independent series of normal, non-muscle invasive (NMIBC) and MIBC tissue samples. Furthermore, expression levels of CAT1297 were found to be correlated with disease-free and overall survival in MIBC. Knockdown of CAT266, CAT1297, and CAT1647 decreased cell viability and colony formation, due to the induction of apoptosis. In conclusion, our data show that lncRNAs expression is de-regulated in MIBC and three aberrantly expressed transcripts regulate proliferation and apoptosis. Our data indicate that lncRNAs play an important role in MIBC development and progression and are a treasure chest for the discovery of new biomarkers.
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