Profiling of long non-coding RNAs identifies LINC00958 and LINC01296 as candidate oncogenes in bladder cancer.
Aberrant expression of long non-coding RNAs (lncRNAs) has been regarded as a critical component in bladder cancer (BC) and lncRNAs have been associated with BC development and progression although their overall expression and functional significance is still unclear. The aim of our study was to identify novel lncRNAs with a functional role in BC carcinogenesis. RNA-sequencing was used to identify aberrantly expressed lncRNAs in 8 normal and 72 BC samples. We identified 89 lncRNAs that were significantly dys-regulated in BC. Five lncRNAs; LINC00958, LINC01296, LINC00355, LNC-CMC1-1 and LNC-ALX1-2 were selected for further analyses. Silencing of LINC00958 or LINC01296 in vitro reduced both cell viability and migration. Knock-down of LINC00958 also affected invasion and resistance to anoikis. These cellular effects could be linked to direct/indirect regulation of protein coding mRNAs involved in cell death/survival, proliferation and cellular movement. Finally, we showed that LINC00958 binds proteins involved in regulation and initiation of translation and in post-transcriptional modification of RNA, including Metadherin, which has previously been associated with BC. Our analyses identified novel lncRNAs in BC that likely act as oncogenic drivers contributing to an aggressive cancerous phenotype likely through interaction with proteins involved in initiation of translation and/or post-transcriptional modification of RNA.
Department of Molecular Medicine, Aarhus University Hospital, University of Aarhus, Aarhus, Denmark.|Department of Urology, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.
Anna Katharina
AK
Seitz
Department of Molecular Medicine, Aarhus University Hospital, University of Aarhus, Aarhus, Denmark.
Lise Lotte
LL
Christensen
Department of Molecular Medicine, Aarhus University Hospital, University of Aarhus, Aarhus, Denmark.
Emil
E
Christensen
Department of Molecular Medicine, Aarhus University Hospital, University of Aarhus, Aarhus, Denmark.
Kasper
K
Faarkrog
Department of Molecular Medicine, Aarhus University Hospital, University of Aarhus, Aarhus, Denmark.
Marie Stampe
MS
Ostenfeld
Department of Molecular Medicine, Aarhus University Hospital, University of Aarhus, Aarhus, Denmark.
Jakob
J
Hedegaard
Department of Molecular Medicine, Aarhus University Hospital, University of Aarhus, Aarhus, Denmark.
Iver
I
Nordentoft
Department of Molecular Medicine, Aarhus University Hospital, University of Aarhus, Aarhus, Denmark.
Morten Muhlig
MM
Nielsen
Research unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University Hospital, University of Aarhus, Aarhus, Denmark.
Johan
J
Palmfeldt
Research unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University Hospital, University of Aarhus, Aarhus, Denmark.
Michelle
M
Thomson
Department of Molecular Biology and Genetics - Genome expression, stability and technology, University of Aarhus, Aarhus, Denmark.
Michael Theis Solgaard
MT
Jensen
Department of Urology, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.
Roman
R
Nawroth
Department of Urology, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.
Tobias
T
Maurer
Department of Molecular Medicine, Aarhus University Hospital, University of Aarhus, Aarhus, Denmark.
Torben Falck
TF
Ørntoft
Department of Urology, Aarhus University Hospital, University of Aarhus, Aarhus, Denmark.
Jørgen Bjerggaard
JB
Jensen
Department of Molecular Biology and Genetics - Genome expression, stability and technology, University of Aarhus, Aarhus, Denmark.
Christian Kroun
CK
Damgaard
Department of Molecular Medicine, Aarhus University Hospital, University of Aarhus, Aarhus, Denmark. lars@clin.au.dk.
Lars
L
Dyrskjøt
D045744:Cell Line, Tumor; D002470:Cell Survival; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009857:Oncogenes; D062085:RNA, Long Noncoding / Q000235:genetics*; D059467:Transcriptome; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
D062085:RNA, Long Noncoding