PMID- 23970374 OWN - NLM STAT- MEDLINE DCOM- 20131126 LR - 20171017 IS - 1545-5017 (Electronic) IS - 1545-5009 (Linking) VI - 60 IP - 12 DP - 2013 Dec TI - Overexpression of miR-708 and its targets in the childhood common precursor B-cell ALL. PG - 2060-7 LID - 10.1002/pbc.24583 [doi] AB - BACKGROUND: The 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). PROCEDURES: To 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. RESULTS: Significant 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 394-400 bp sequence region of the 3'-UTR of CNTFR mRNA. CONCLUSION: The 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. CI - (c) 2013 Wiley Periodicals, Inc. FAU - Li, Xue AU - Li X AD - Department of Pediatrics, Cryomedicine Laboratory, Qilu Hospital, Shandong University, Shandong, PR China. FAU - Li, Dong AU - Li D FAU - Zhuang, Yong AU - Zhuang Y FAU - Shi, Qing AU - Shi Q FAU - Wei, Wei AU - Wei W FAU - Ju, Xiuli AU - Ju X LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Retracted Publication DEP - 20130823 PL - United States TA - Pediatr Blood Cancer JT - Pediatric blood & cancer JID - 101186624 RN - 0 (CNTFR protein, human) RN - 0 (Ciliary Neurotrophic Factor Receptor alpha Subunit) RN - 0 (GNG2 protein, human) RN - 0 (MIRN708 microRNA, human) RN - 0 (Membrane Proteins) RN - 0 (MicroRNAs) RN - 0 (NNAT protein, human) RN - 0 (Nerve Tissue Proteins) RN - EC 3.6.1.- (GTP-Binding Proteins) SB - IM CIN - Pediatr Blood Cancer. 2015 Jan;62(1):177-8. PMID: 25214155 RIN - Pediatr Blood Cancer. 2017 May;64(5):null. PMID: 28342301 MH - Blotting, Western MH - Child MH - Child, Preschool MH - Ciliary Neurotrophic Factor Receptor alpha Subunit/biosynthesis/genetics MH - Female MH - GTP-Binding Proteins/biosynthesis/genetics MH - Gene Expression Regulation, Neoplastic/*genetics MH - Humans MH - Infant MH - Male MH - Membrane Proteins/biosynthesis/genetics MH - MicroRNAs/*biosynthesis/genetics MH - Microarray Analysis MH - Nerve Tissue Proteins/biosynthesis/genetics MH - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*genetics MH - Real-Time Polymerase Chain Reaction MH - Up-Regulation OTO - NOTNLM OT - miRNA OT - pediatric acute lymphoblastic leukemia OT - regulatory region OT - target gene EDAT- 2013/08/24 06:00 MHDA- 2013/12/16 06:00 CRDT- 2013/08/24 06:00 PHST- 2013/01/08 00:00 [received] PHST- 2013/04/07 00:00 [accepted] PHST- 2013/08/24 06:00 [entrez] PHST- 2013/08/24 06:00 [pubmed] PHST- 2013/12/16 06:00 [medline] AID - 10.1002/pbc.24583 [doi] PST - ppublish SO - Pediatr Blood Cancer. 2013 Dec;60(12):2060-7. doi: 10.1002/pbc.24583. Epub 2013 Aug 23.