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MicroRNA 34b inhibits cell proliferation in pediatric acute myeloid leukemia via regulating LDHA.

小RNA 髓系白血病 细胞周期 乳酸脱氢酶A 流式细胞术 细胞凋亡 癌症研究 白血病 实时聚合酶链反应 细胞生长 生物 医学 分子生物学 乳酸脱氢酶 免疫学 基因 生物化学
作者
Qi Hx,Cao Q,Zhou Gp,Sun Xz,Zhou Wd,Zhanying Hong,Jim Hu,Juan Cx,Li S,Kuai Wx
出处
期刊:PubMed 卷期号:23 (12): 5351-5359 被引量:3
标识
DOI:10.26355/eurrev_201906_18202
摘要

To elucidate the regulatory effect of microRNA-34b on the occurrence of pediatric acute myeloid leukemia and the underlying mechanism.The expression of microRNA-34b in the bone marrow of 72 children with newly diagnosed acute myeloid leukemia (AML) was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between microRNA-34b expression and pathological characteristics was analyzed. Kaplan-Meier curve was introduced for evaluating the prognostic value of microRNA-34b in pediatric AML. The regulatory effects of microRNA-34b on proliferation, cell cycle, and apoptosis of leukemia cells were accessed by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. Bioinformatics prediction and dual-luciferase reporter gene assay were conducted to evaluate the binding between microRNA-34b and lactate dehydrogenase A (LDHA). LDHA expression after overexpression of microRNA-34b was determined by qRT-PCR and Western blot. Rescue experiments were conducted to verify whether microRNA-34b could regulate proliferative and apoptotic behaviors of leukemia cells by suppressing LDHA expression.MicroRNA-34b was markedly downregulated in AML children. Low expression of microRNA-34b was correlated to FAB typing, cytogenetic abnormality, and day 7 response to the treatment of pediatric AML. By collecting the follow-up data, it was found that low expression of microRNA-34b was correlated to the poor prognosis of AML. Overexpression of microRNA-34b inhibited proliferative ability and cell cycle progression, but accelerated apoptosis of AML cells. Dual-luciferase reporter gene assay verified that microRNA-34b could bind to LDHA, thereafter inhibiting LDHA expression. Overexpression of LDHA reversed the regulatory effects of microRNA-34b on proliferation, cell cycle, and apoptosis of AML cells.We found that microRNA-34b is lowly expressed in pediatric AML patients, and low expression of microRNA-34b may serve as an indicator of malignant progression and poor prognosis of pediatric AML. MicroRNA-34b may affect the proliferation and apoptosis of leukemia cells by regulating the expression of LDHA.

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