Xiang Wang1, Dongjian Zuo2, Yufang Yuan1, Xiaochun Yang1, Ze Hong1, Rongrong Zhang3. 1. Department of Pediatrics, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, 223300, Jiangsu, China. 2. Department of Neurosurgery, Huai'an Hospital Affiliated to Xuzhou Medical College and Huai'an Second People's Hospital, 62 Huaihai Road South, Huai'an, 223002, Jiangsu, China. 3. Department of Pediatrics, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, 223300, Jiangsu, China. zrrhayy@sina.com.
Abstract
PURPOSE: The aim of this study was to investigate roles of microRNA (miR)-183 in pediatric acute myeloid leukemia (AML). METHODS: miR-183 expression in bone marrow and patients' sera of childhood AML was detected by real-time quantitative PCR. Functions of miR-183 in malignant phenotypes of two leukemia cell lines were then evaluated. Additionally, putative targets of miR-183 were predicted using three miRNA target prediction algorithms and validated by luciferase reporter assay. Clinical relevance of miR-183 and its target gene were further determined. RESULTS: miR-183 expression in bone marrow and patients' sera of childhood AML was both significantly higher than those in the corresponding normal controls (both P < 0.001). Enforced expression of miR-183 dramatically enhanced cell proliferation and G1/S transition, but inhibited cell apoptosis of leukemia cells. Bioinformatics prediction and luciferase reporter assay identified programmed cell death 6 (PDCD6) as a direct target gene of miR-183. Moreover, high serum miR-183 combined with low serum PDCD6 mRNA was significantly associated with French-American-British classification subtype M7 (P = 0.01) and unfavorable karyotypes (P = 0.006). Further multivariate analysis identified the combination of serum miR-183 and PDCD6 levels as an independent prognostic factor for both relapse-free and overall survivals. Functionally, re-introduction of PDCD6 markedly reversed the effects of miR-183 in cell cycle, proliferation and apoptosis of two leukemia cell lines. CONCLUSION: Combined serum miR-183 and PDCD6 mRNA may serve as a novel prognostic biomarker for pediatric AML. Interestingly, miR-183 may function as an oncogene and may enhance cell proliferation by targeting PDCD6, implying a potential therapeutic target for this malignancy.
PURPOSE: The aim of this study was to investigate roles of microRNA (miR)-183 in pediatric acute myeloid leukemia (AML). METHODS:miR-183 expression in bone marrow and patients' sera of childhood AML was detected by real-time quantitative PCR. Functions of miR-183 in malignant phenotypes of two leukemia cell lines were then evaluated. Additionally, putative targets of miR-183 were predicted using three miRNA target prediction algorithms and validated by luciferase reporter assay. Clinical relevance of miR-183 and its target gene were further determined. RESULTS:miR-183 expression in bone marrow and patients' sera of childhood AML was both significantly higher than those in the corresponding normal controls (both P < 0.001). Enforced expression of miR-183 dramatically enhanced cell proliferation and G1/S transition, but inhibited cell apoptosis of leukemia cells. Bioinformatics prediction and luciferase reporter assay identified programmed cell death 6 (PDCD6) as a direct target gene of miR-183. Moreover, high serum miR-183 combined with low serum PDCD6 mRNA was significantly associated with French-American-British classification subtype M7 (P = 0.01) and unfavorable karyotypes (P = 0.006). Further multivariate analysis identified the combination of serum miR-183 and PDCD6 levels as an independent prognostic factor for both relapse-free and overall survivals. Functionally, re-introduction of PDCD6 markedly reversed the effects of miR-183 in cell cycle, proliferation and apoptosis of two leukemia cell lines. CONCLUSION: Combined serum miR-183 and PDCD6 mRNA may serve as a novel prognostic biomarker for pediatric AML. Interestingly, miR-183 may function as an oncogene and may enhance cell proliferation by targeting PDCD6, implying a potential therapeutic target for this malignancy.
Authors: Wei Gu; Tian Gao; Jie Shen; Ying Sun; Xiong Zheng; Ji Wang; Jin Ma; Xiao-Ying Hu; Jian Li; Mei-Jie Hu Journal: Int J Clin Exp Med Date: 2014-09-15
Authors: David M Garcia; Daehyun Baek; Chanseok Shin; George W Bell; Andrew Grimson; David P Bartel Journal: Nat Struct Mol Biol Date: 2011-09-11 Impact factor: 15.369