Identification of long non-coding RNAs that stimulate cell survival in bladder cancer

// Aleksandra M. Dudek 1 , Sabrina J. Boer 1 , Nanda Boon 1 , J. Alfred Witjes 1 , Lambertus A.L.M. Kiemeney 1, 2 , Gerald W. Verhaegh 1 1 Department of Urology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands 2 Department for Health Evidence, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands Correspondence to: 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 ABSTRACT 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.