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

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.

Attenuating the abnormally high expression of AEBP1 suppresses the pathogenesis of childhood acute lymphoblastic leukemia via p53-dependent signaling pathway.

OBJECTIVE: This study aimed to explore the candidate genes and their potential mechanism in childhood acute lymphoblastic leukemia (cALL). MATERIALS AND METHODS: Differentially expressed genes (DEGs) were screened from GSE67684 (treatment), GSE28460 (relapse), and GSE60926 (relapse). The expression of AEBP1 at different stages of cALL was analyzed followed by functional enrichment analysis of its co-expressed genes. Expression of AEBP1 was determined in different leukemia cell lines and knocked down in Jurkat cells. Cell behaviors as well as the expression of p53, Bax, and Bcl-2 were also evaluated after silencing AEBP1 in Jurkat cells. RESULTS: Two clusters: Profile 1 (downward) and Profile 26 (upward) were identified in GSE67684, and 53 Profile 1-specific DEGs were identified compared with DEGs in GSE28460 and GSE60926. AEBP1 was one of these genes and was significantly downregulated after treatment but upregulated in relapse samples. Functional enrichment analysis revealed that AEBP1 co-expressed genes were significantly enriched in GO terms including immune response, blood coagulation etc. and in the hematopoietic cell lineage and PI3K/Akt signaling pathways. AEBP1 was significantly increased in leukemia cell lines, especially in Jurkat cells, compared with the Pbmc cells. Silencing AEBP1 markedly reduced proliferation and induced cell cycle arrest in Jurkat cells, but also promoted apoptosis of Jurkat cells. Silencing AEBP1 also inhibited the expression of p53 and Bcl-2 but promoted Bax in Jurkat cells. CONCLUSIONS: AEBP1 was highly-expressed in the diagnosis and relapse cALL, and silencing AEBP1 significantly reduced proliferation but promoted apoptosis in Jurkat cells via a p53-dependent pathway.