Downregulation of miRNA-133a and miRNA-452 associated with upregulation of CLNK and LEF1 genes in chronic lymphocytic leukemia: in vitro and in silico insights.
[BACKGROUND] Chronic lymphocytic leukemia (CLL), a common B-cell malignancy, exhibits diverse clinical outcomes influenced by microRNA (miRNA) dysregulation.
- p-value p < 0.001
APA
Dalyan A, Özaslan M, et al. (2025). Downregulation of miRNA-133a and miRNA-452 associated with upregulation of CLNK and LEF1 genes in chronic lymphocytic leukemia: in vitro and in silico insights.. Molecular biology reports, 53(1), 50. https://doi.org/10.1007/s11033-025-11203-w
MLA
Dalyan A, et al.. "Downregulation of miRNA-133a and miRNA-452 associated with upregulation of CLNK and LEF1 genes in chronic lymphocytic leukemia: in vitro and in silico insights.." Molecular biology reports, vol. 53, no. 1, 2025, pp. 50.
PMID
41191156
Abstract
[BACKGROUND] Chronic lymphocytic leukemia (CLL), a common B-cell malignancy, exhibits diverse clinical outcomes influenced by microRNA (miRNA) dysregulation. This study investigates the expression and regulatory roles of miRNA-133a and miRNA-452 in CLL.
[METHODS AND RESULTS] Peripheral blood samples from 63 CLL patients and 50 age-matched healthy controls were analyzed using quantitative real-time PCR (qRT-PCR), revealing significant downregulation of miRNA-133a and miRNA-452 in patients compared to controls (p < 0.001). Concurrently, predicted target genes CLNK and LEF1 were upregulated (p < 0.001). Age-stratified analysis showed lower miRNA-133a and miRNA-452 expression in patients aged ≤ 55 years versus > 55 years (p = 0.034 and p = 0.033, respectively). In silico analyses using miRTarBase, TargetScan, and GEO2R (GSE22529) confirmed regulatory interactions between miRNA-133a and CLNK, and miRNA-452 and LEF1, with CpG island hypermethylation (GSE151010) potentially contributing to miRNA downregulation. Competing endogenous RNA (ceRNA) networks involving MALAT1, CDR1as, NEAT1, and PTEN were identified, suggesting miRNA sequestration.
[CONCLUSIONS] These findings indicate that miRNA-133a and miRNA-452 downregulation, coupled with CLNK and LEF1 upregulation, may drive CLL pathogenesis, with age-related differences highlighting their potential as diagnostic biomarkers. Further validation in larger cohorts and functional studies are warranted to elucidate their mechanistic roles.
[METHODS AND RESULTS] Peripheral blood samples from 63 CLL patients and 50 age-matched healthy controls were analyzed using quantitative real-time PCR (qRT-PCR), revealing significant downregulation of miRNA-133a and miRNA-452 in patients compared to controls (p < 0.001). Concurrently, predicted target genes CLNK and LEF1 were upregulated (p < 0.001). Age-stratified analysis showed lower miRNA-133a and miRNA-452 expression in patients aged ≤ 55 years versus > 55 years (p = 0.034 and p = 0.033, respectively). In silico analyses using miRTarBase, TargetScan, and GEO2R (GSE22529) confirmed regulatory interactions between miRNA-133a and CLNK, and miRNA-452 and LEF1, with CpG island hypermethylation (GSE151010) potentially contributing to miRNA downregulation. Competing endogenous RNA (ceRNA) networks involving MALAT1, CDR1as, NEAT1, and PTEN were identified, suggesting miRNA sequestration.
[CONCLUSIONS] These findings indicate that miRNA-133a and miRNA-452 downregulation, coupled with CLNK and LEF1 upregulation, may drive CLL pathogenesis, with age-related differences highlighting their potential as diagnostic biomarkers. Further validation in larger cohorts and functional studies are warranted to elucidate their mechanistic roles.
MeSH Terms
Humans; MicroRNAs; Lymphoid Enhancer-Binding Factor 1; Leukemia, Lymphocytic, Chronic, B-Cell; Middle Aged; Female; Male; Down-Regulation; Aged; Up-Regulation; DNA Methylation; Gene Expression Regulation, Leukemic; Gene Expression Regulation, Neoplastic; Computer Simulation; CpG Islands; Adult; Case-Control Studies; Gene Regulatory Networks