Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas.
Noncoding RNA (ncRNA) transcripts are thought to be involved in human tumorigenesis. We report that a large fraction of genomic ultraconserved regions (UCRs) encode a particular set of ncRNAs whose expression is altered in human cancers. Genome-wide profiling revealed that UCRs have distinct signatures in human leukemias and carcinomas. UCRs are frequently located at fragile sites and genomic regions involved in cancers. We identified certain UCRs whose expression may be regulated by microRNAs abnormally expressed in human chronic lymphocytic leukemia, and we proved that the inhibition of an overexpressed UCR induces apoptosis in colon cancer cells. Our findings argue that ncRNAs and interaction between noncoding genes are involved in tumorigenesis to a greater extent than previously thought.
Calin
George A
GA
Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA.
Liu
Chang-gong
CG
Ferracin
Manuela
M
Hyslop
Terry
T
Spizzo
Riccardo
R
Sevignani
Cinzia
C
Fabbri
Muller
M
Cimmino
Amelia
A
Lee
Eun Joo
EJ
Wojcik
Sylwia E
SE
Shimizu
Masayoshi
M
Tili
Esmerina
E
Rossi
Simona
S
Taccioli
Cristian
C
Pichiorri
Flavia
F
Liu
Xiuping
X
Zupo
Simona
S
Herlea
Vlad
V
Gramantieri
Laura
L
Lanza
Giovanni
G
Alder
Hansjuerg
H
Rassenti
Laura
L
Volinia
Stefano
S
Schmittgen
Thomas D
TD
Kipps
Thomas J
TJ
Negrini
Massimo
M
Croce
Carlo M
CM
D001483:Base Sequence; D002277:Carcinoma / Q000235:genetics*; D016000:Cluster Analysis; D017124:Conserved Sequence; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D035683:MicroRNAs / Q000502:physiology; D008969:Molecular Sequence Data; D009857:Oncogenes / Q000502:physiology; D022661:RNA, Untranslated / Q000737:chemistry*; D017423:Sequence Analysis, RNA