TY - JOUR
T1 - Profiling of long non-coding RNAs identifies LINC00958 and LINC01296 as candidate oncogenes in bladder cancer
AU - Seitz, Anna Katharina
AU - Christensen, Lise Lotte
AU - Christensen, Emil
AU - Faarkrog, Kasper
AU - Ostenfeld, Marie Stampe
AU - Hedegaard, Jakob
AU - Nordentoft, Iver
AU - Nielsen, Morten Muhlig
AU - Palmfeldt, Johan
AU - Thomson, Michelle
AU - Jensen, Michael Theis Solgaard
AU - Nawroth, Roman
AU - Maurer, Tobias
AU - Orntoft, Torben Falck
AU - Jensen, Jorgen Bjerggaard
AU - Damgaard, Christian Kroun
AU - Dyrskjot, Lars
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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, LNCCMC1-1 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.
AB - 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, LNCCMC1-1 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.
KW - UROTHELIAL CARCINOMA
KW - TUMOR-SUPPRESSOR
KW - UP-REGULATION
KW - CELL-LINES
KW - EXPRESSION
KW - HOTAIR
KW - METASTASIS
KW - SIGNATURE
KW - EVOLUTION
KW - REVEALS
UR - http://www.scopus.com/inward/record.url?scp=85016796932&partnerID=8YFLogxK
U2 - 10.1038/s41598-017-00327-0
DO - 10.1038/s41598-017-00327-0
M3 - Journal article
C2 - 28341852
SN - 2045-2322
VL - 7
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 395
ER -