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: Yue Liu, Wenling Zheng, Yanbin Song, Wenli Ma, Hong Yin
• Journal: PloS one (PLoS One) Vol. 8 Issue 7 Pg. e68442 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23894305 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Homeodomain Proteins
• MIRN196 microRNA, human
• MicroRNAs
• homeobox protein HOXA9
• Fusion Proteins, bcr-abl

Topics

• Cell Line, Tumor
• Cell Transformation, Neoplastic (genetics)
• CpG Islands
• DNA Methylation
• Fusion Proteins, bcr-abl (genetics)
• Gene Expression
• Gene Expression Regulation, Leukemic
• Genes, Reporter
• Homeodomain Proteins (genetics)
• Humans
• K562 Cells
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (genetics)
• MicroRNAs (genetics)
• Promoter Regions, Genetic
• RNA Interference
• Reproducibility of Results