An integrative genomics screen uncovers ncRNA T-UCR functions in neuroblastoma tumours.
Different classes of non-coding RNAs, including microRNAs, have recently been implicated in the process of tumourigenesis. In this study, we examined the expression and putative functions of a novel class of non-coding RNAs known as transcribed ultraconserved regions (T-UCRs) in neuroblastoma. Genome-wide expression profiling revealed correlations between specific T-UCR expression levels and important clinicogenetic parameters such as MYCN amplification status. A functional genomics approach based on the integration of multi-level transcriptome data was adapted to gain insights into T-UCR functions. Assignments of T-UCRs to cellular processes such as TP53 response, differentiation and proliferation were verified using various cellular model systems. For the first time, our results define a T-UCR expression landscape in neuroblastoma and suggest widespread T-UCR involvement in diverse cellular processes that are deregulated in the process of tumourigenesis.
Mestdagh
P
P
Center for Medical Genetics, Ghent University Hospital, Ghent, East-Flanders, Belgium.
Fredlund
E
E
Pattyn
F
F
Rihani
A
A
Van Maerken
T
T
Vermeulen
J
J
Kumps
C
C
Menten
B
B
De Preter
K
K
Schramm
A
A
Schulte
J
J
Noguera
R
R
Schleiermacher
G
G
Janoueix-Lerosey
I
I
Laureys
G
G
Powel
R
R
Nittner
D
D
Marine
J-C
JC
Ringnér
M
M
Speleman
F
F
Vandesompele
J
J
D045744:Cell Line, Tumor; D017124:Conserved Sequence / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics; D006657:Histones / Q000378:metabolism; D006801:Humans; D009447:Neuroblastoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics*; D022661:RNA, Untranslated / Q000096:biosynthesis / Q000235:genetics*; D015203:Reproducibility of Results; D014158:Transcription, Genetic
D006657:Histones; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D022661:RNA, Untranslated