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Low expression of miR-196b enhances the expression of BCR-ABL1 and HOXA9 oncogenes in chronic myeloid leukemogenesis.

Liu Y, Zheng W, Song Y, Ma W, Yin H - PLoS ONE (2013)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Genetic Engineering, Southern Medical University, Guangzhou, China.

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.

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MiR-196b expression and CpG island methylation.(A) MiR-196b expression levels were significantly lower in CML patients than in healthy controls. (B) Predicted miR-196b promoter CpG islands, obtained from CpG Island Searcher software. (C) The BSP detection method demonstrated decreased methylation after treatment. (D) MSP test results for 45 patients with leukemia and 10 healthy controls. N represents the healthy controls.
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pone-0068442-g001: MiR-196b expression and CpG island methylation.(A) MiR-196b expression levels were significantly lower in CML patients than in healthy controls. (B) Predicted miR-196b promoter CpG islands, obtained from CpG Island Searcher software. (C) The BSP detection method demonstrated decreased methylation after treatment. (D) MSP test results for 45 patients with leukemia and 10 healthy controls. N represents the healthy controls.

Mentions: The average expression level of miR-196b was significantly lower (P<0.001) in the bone marrow samples from the 16 CML patients compared with the 10 healthy controls, as indicated by the RT-qPCR (Figure 1A). In light of this, we investigated the role of epigenetic mechanisms that may be involved in the silencing of miR-196b. A CpG island, similar to that present in many tumor suppressor genes, was found in the 1000 bases upstream from the transcription start site of miR-196b (Figure 1B).


Low expression of miR-196b enhances the expression of BCR-ABL1 and HOXA9 oncogenes in chronic myeloid leukemogenesis.

Liu Y, Zheng W, Song Y, Ma W, Yin H - PLoS ONE (2013)

MiR-196b expression and CpG island methylation.(A) MiR-196b expression levels were significantly lower in CML patients than in healthy controls. (B) Predicted miR-196b promoter CpG islands, obtained from CpG Island Searcher software. (C) The BSP detection method demonstrated decreased methylation after treatment. (D) MSP test results for 45 patients with leukemia and 10 healthy controls. N represents the healthy controls.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3716876&req=5

pone-0068442-g001: MiR-196b expression and CpG island methylation.(A) MiR-196b expression levels were significantly lower in CML patients than in healthy controls. (B) Predicted miR-196b promoter CpG islands, obtained from CpG Island Searcher software. (C) The BSP detection method demonstrated decreased methylation after treatment. (D) MSP test results for 45 patients with leukemia and 10 healthy controls. N represents the healthy controls.
Mentions: The average expression level of miR-196b was significantly lower (P<0.001) in the bone marrow samples from the 16 CML patients compared with the 10 healthy controls, as indicated by the RT-qPCR (Figure 1A). In light of this, we investigated the role of epigenetic mechanisms that may be involved in the silencing of miR-196b. A CpG island, similar to that present in many tumor suppressor genes, was found in the 1000 bases upstream from the transcription start site of miR-196b (Figure 1B).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Genetic Engineering, Southern Medical University, Guangzhou, China.

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.

Show MeSH
Related in: MedlinePlus