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.