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: W Valleron, E Laprevotte, E-F Gautier, C Quelen, C Demur, E Delabesse, X Agirre, F Prósper, T Kiss, P Brousset
• Journal: Leukemia (Leukemia) Vol. 26 Issue 9 Pg. 2052-60 (Sep 2012) ISSN: 1476-5551 [Electronic] England
• PMID: 22522792 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Calcium-Binding Proteins
• DLK1 protein, human
• Intercellular Signaling Peptides and Proteins
• Membrane Proteins
• Oncogene Proteins, Fusion
• RNA, Messenger
• RNA, Small Nucleolar
• promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein

Topics

• Biomarkers, Tumor (genetics, metabolism)
• Blast Crisis
• Blotting, Western
• Calcium-Binding Proteins
• Cell Cycle
• Cell Differentiation
• Cell Proliferation
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Intercellular Signaling Peptides and Proteins (genetics, metabolism)
• Leukemia, Myeloid, Acute (genetics, metabolism)
• Leukemia, Promyelocytic, Acute (genetics, metabolism)
• Membrane Proteins (genetics, metabolism)
• Oligonucleotide Array Sequence Analysis
• Oncogene Proteins, Fusion (genetics, metabolism)
• RNA, Messenger (genetics)
• RNA, Small Nucleolar (genetics, metabolism)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Cells, Cultured