Journal
PEDIATRIC BLOOD & CANCER
Volume 60, Issue 12, Pages 2060-2067Publisher
WILEY
DOI: 10.1002/pbc.24583
Keywords
miRNA; pediatric acute lymphoblastic leukemia; regulatory region; target gene
Categories
Funding
- Shandong Province Natural Science Foundation [ZR2011HM007, 2010G0020213]
- Major State Basic Research Development Program [2012CB96650481102710]
- Innovation Fund Project of Shandong University [2012ZD023]
Ask authors/readers for more resources
BackgroundThe critical function of microRNAs in the pathogenesis and prognosis of hematopoietic cancer has become increasingly apparent. However, only a few miRNAs have been reported to be altered in acute lymphocytic leukemia (ALL). ProceduresTo uncover aberrantly expressed miRNAs in pediatric B-cell ALL, our study employed genome-wide miRNA microarray analysis and stem-loop real-time quantitative polymerase chain reaction (qRT-PCR) to examine common precursor B-cell ALL samples. The target genes of miRNA-708 were then identified and verified by bioinformatics, dual-luciferase reporter assay, qRT-PCR, and Western blot. ResultsSignificant upregulation of miR-708, miR-210, and miR-181b, and downregulation of miR-345 and miR-27a were observed in common precursor B-cell ALL (common-ALL) samples (P<0.05). In addition, elevated expression of miR-708 and miR-181b were found in high-risk common-ALL compared to standard and intermediate ones. miR-708 inhibited luciferase reporter activity by binding to the 3-untranslated regions (3-UTRs) of CNTFR, NNAT, and GNG12 mRNA in HEK-293 cell line and suppressed the protein levels of CNTFR, NNAT, and GNG12 in Jurkat cells. In addition, mRNA levels of CNTFR and NNAT, but not of GNG12, were found to be downregulated in high risk common-ALL samples. Mutational analysis revealed that miR-708 binds to the 394-400bp sequence region of the 3-UTR of CNTFR mRNA. ConclusionThe expression level of miR-708 reflects differences among the clinical types of common-ALL, and CNTFR, NNAT, and GNG12 were identified as targets of miR-708. Pediatr Blood Cancer 2013;60:2060-2067. (c) 2013 Wiley Periodicals, Inc.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available