1. MicroRNA 34b inhibits cell proliferation in pediatric acute myeloid leukemia via regulating LDHA.
- Author
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Qi HX, Cao Q, Zhou GP, Sun XZ, Zhou WD, Hong Z, Hu J, Juan CX, Li S, and Kuai WX
- Subjects
- Apoptosis genetics, Bone Marrow pathology, Cell Cycle genetics, Cell Line, Tumor, Cell Proliferation genetics, Child, Child, Preschool, Disease Progression, Down-Regulation, Female, Follow-Up Studies, Humans, Kaplan-Meier Estimate, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute pathology, Male, Prognosis, Gene Expression Regulation, Leukemic, L-Lactate Dehydrogenase genetics, Leukemia, Myeloid, Acute genetics, MicroRNAs metabolism
- Abstract
Objective: To elucidate the regulatory effect of microRNA-34b on the occurrence of pediatric acute myeloid leukemia and the underlying mechanism., Patients and Methods: 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., Results: 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., Conclusions: 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.
- Published
- 2019
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