title: Specific small nucleolar RNA expression profiles in acute leukemia.
abstract: Apart from microRNAs, little is known about the regulation of expression of non-coding RNAs in cancer. We investigated whether small nucleolar RNAs (snoRNAs) accumulation displayed specific signatures in acute myeloblastic and acute lymphoblastic leukemias. Using microarrays and high-throughput quantitative PCR (qPCR), we demonstrate here that snoRNA expression patterns are negatively altered in leukemic cells compared with controls. Interestingly, a specific signature was found in acute promyelocytic leukemia (APL) with ectopic expression of SNORD112-114 snoRNAs located at the DLK1-DIO3 locus. In vitro experiments carried out on APL blasts demonstrate that transcription of these snoRNAs was lost under all-trans retinoic acid-mediated differentiation and induced by enforced expression of the PML-RARalpha fusion protein in negative leukemic cell lines. Further experiments revealed that the SNORD114-1 (14q(II-1)) variant promoted cell growth through cell cycle modulation; its expression was implicated in the G0/G1 to S phase transition mediated by the Rb/p16 pathways. This study thus reports three important observations: (1) snoRNA regulation is different in normal cells compared with cancer cells; (2) a relationship exists between a chromosomal translocation and expression of snoRNA loci; and (3) snoRNA expression can affect Rb/p16 cell cycle regulation. Taken together, these data strongly suggest that snoRNAs have a role in cancer development.
authors.affiliation: INSERM UMR1037-Cancer Research Center of Toulouse, University of Toulouse III, Toulouse, France.
authors.forename: W
authors.initials: W
authors.lastname: Valleron
authors.forename: E
authors.initials: E
authors.lastname: Laprevotte
authors.forename: E-F
authors.initials: EF
authors.lastname: Gautier
authors.forename: C
authors.initials: C
authors.lastname: Quelen
authors.forename: C
authors.initials: C
authors.lastname: Demur
authors.forename: E
authors.initials: E
authors.lastname: Delabesse
authors.forename: X
authors.initials: X
authors.lastname: Agirre
authors.forename: F
authors.initials: F
authors.lastname: Prósper
authors.forename: T
authors.initials: T
authors.lastname: Kiss
authors.forename: P
authors.initials: P
authors.lastname: Brousset
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001752:Blast Crisis; D015153:Blotting, Western; D002135:Calcium-Binding Proteins; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020537:RNA, Small Nucleolar / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; D020537:RNA, Small Nucleolar; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein