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. 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.