Hypermethylation of microRNA-34c CpG Island predicts unfavorable prognosis in acute myeloid leukemia
Year: 2025
Type: article
Study design: Observational Study
Abstract: PurposeResearches have found that the expression of microRNAs is regulated by CpG island hypermethylation in acute myeloid leukemia (AML). The deregulation of microRNA-34c (miR-34c) caused by CpG island methylation has been demonstrated in a few cancers and miR-34c has been shown to be part of the P53 pathway. However, the potential role of miR-34c CpG island methylation in AML remains to be elucidated.MethodsQuantitative Real-time MSP (qRT-MSP) was carried out to detect miR-34c CpG island methylation status in 205 de novo AML patients and 51 healthy controls. Quantitative Real-time PCR was carried out to detect miR-34c expression. MiR-34c-mimics were transfected into THP-1 cells lines. Cell viability after transfection was detected by cell counting Kit-8 assays. Flow cytometry was used to detect apoptosis. Western blot analysis was used to detected the protein expression of p53.ResultsWe found the down-regulation of miR-34c was associated with hypermethylation of the neighboring CpG island, and decitabine treatment rapidly restored miR-34c expression. Hypermethylation of the miR-34c CpG island was frequently observed in primary AML patients' bone marrow but not in healthy donors’. Hypermethylation of the miR-34c CpG island correlated with shorter overall survival and was further confirmed by multivariate analyses. Moreover, we detected 15 AML patients who received decitabine and achieved complete remission, and we found that methylation of miR-34c CpG island significantly decreased and expression of miR-34c significantly increased. MiR-34c CpG island hypermethylation group was positively associated with the presence of P53 (P =0.018) and TET2 mutations (P = 0.025) but inversely correlated with CEBPA (P = 0.029). Interestingly, the p53 protein expression level was increased with miR-34c CpG island demethylating. And enhancing miR-34c expression in THP-1 cells showed the same results.ConclusionsOur results suggested that miR-34c CpG island regulates miR-34c expression and hypermethylation of miR-34c CpG island is a frequent target of epigenetic silencing in AML. Moreover, there is positive feedback exists between miR-34c demethylation and p53 protein expression.
Source: Scientific Reports
Authors: Dongqin Yang, Meng Yan, Jian Guo, Lingyun Wu
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,690
OpenAlex ID: W4414933565