1. Clinical significance of microRNA-34b expression in pediatric acute leukemia
- Author
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Shaoyan Hu, Yi-huan Chai, Yi Wang, Hailong He, Wenli Zhao, Na Wang, Guixiong Gu, Jian Pan, and Lan Cao
- Subjects
Male ,0301 basic medicine ,Cancer Research ,Adolescent ,Cell ,Down-Regulation ,HL-60 Cells ,Biology ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Line, Tumor ,hemic and lymphatic diseases ,Genetics ,medicine ,Humans ,Child ,Promoter Regions, Genetic ,Molecular Biology ,Cell Proliferation ,Acute leukemia ,Gene Expression Regulation, Leukemic ,Cell growth ,Infant ,Myeloid leukemia ,Methylation ,DNA Methylation ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Cell cycle ,Demethylating agent ,Leukemia, Myeloid, Acute ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,chemistry ,Case-Control Studies ,Child, Preschool ,030220 oncology & carcinogenesis ,Immunology ,Cancer research ,Molecular Medicine ,CpG Islands ,Female ,RNA Interference ,K562 Cells ,K562 cells - Abstract
The present study aimed to explore the function of miR‑34b promoter methylation in cell proliferation in children's acute leukemia. Quantitative PCR and methylation‑specific PCR were performed to measure the levels of miR‑34b and its promoter methylation in normal cells, eight leukemia cell lines as well as primary leukemic cells isolated from patients newly diagnosed with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) and mixed lymphocytic lymphoma. miR‑34b levels in leukemia cell lines and primary leukemic cells were significantly lower than those in normal cells. The miR‑34b promoter was found to be methylated in all leukemia cell lines, 24 of 31 ALL patients and 8 of 19 AML patients, but not in the 23 normal controls. miR‑34b expression and methylation of its promoter were not associated with most clinical parameters assessed; however, miR‑34b levels in prednisone‑sensitive ALL were significantly different from those in insensitive ALL. A cell counting kit‑8 assay showed that transfection of miR‑34b mimics into K562 cells inhibited their proliferation. Furthermore, treatment with the demethylating agent 5‑aza‑2‑deoxycytidine significantly enhanced miR‑34b expression levels and decreased the methylation status of its promoter in HL‑60 and K562 cells. In conclusion, the results of the present study indicated that in pediatric leukemia cells and leukemia cell lines, the expression of miR‑34b is inhibited by methylation of its promoter, which impairs the restraining effects of miR‑34b on cell proliferation. It was also indicated that the expression of miR‑34b in ALL patients may affect their response to early treatments.
- Published
- 2016