title: Low expression of miR-196b enhances the expression of BCR-ABL1 and HOXA9 oncogenes in chronic myeloid leukemogenesis.
abstract: MicroRNAs (miRNAs) can function as tumor suppressors or oncogene promoters during tumor development. In this study, low levels of expression of miR-196b were detected in patients with chronic myeloid leukemia. Bisulfite genomic sequencing PCR and methylation-specific PCR were used to examine the methylation status of the CpG islands in the miR-196b promoter in K562 cells, patients with leukemia and healthy individuals. The CpG islands showed more methylation in patients with chronic myeloid leukemia compared with healthy individuals (P<0.05), which indicated that low expression of miR-196b may be associated with an increase in the methylation of CpG islands. The dual-luciferase reporter assay system demonstrated that BCR-ABL1 and HOXA9 are the target genes of miR-196b, which was consistent with predictions from bioinformatics software analyses. Further examination of cell function indicated that miR-196b acts to reduce BCR-ABL1 and HOXA9 protein levels, decrease cell proliferation rate and retard the cell cycle. A low level of expression of miR-196b can cause up-regulation of BCR-ABL1 and HOXA9 expression, which leads to the development of chronic myeloid leukemia. MiR-196b may represent an effective target for chronic myeloid leukemia therapy.
authors.affiliation: Institute of Genetic Engineering, Southern Medical University, Guangzhou, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.forename: Wenling
authors.initials: W
authors.lastname: Zheng
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Song
authors.forename: Wenli
authors.initials: W
authors.lastname: Ma
authors.forename: Hong
authors.initials: H
authors.lastname: Yin
mesh_terms: D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D015870:Gene Expression; D015973:Gene Expression Regulation, Leukemic; D017930:Genes, Reporter; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D015203:Reproducibility of Results
chemical_list: D018398:Homeodomain Proteins; C542543:MIRN196 microRNA, human; D035683:MicroRNAs; C097899:homeobox protein HOXA9; D016044:Fusion Proteins, bcr-abl
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