Differential expression analysis of miRNAs and identification of potential key genes in pediatric T-cell acute lymphoblastic leukemia

Pediatric T-cell Acute Lymphoblastic Leukemia (T-ALL) is an aggressive form of ALL comprising 15–20% of cases, characterized by malignant transformation of progenitor T-cells. Numerous genetic and epigenetic alterations have been identified as key contributor of this transformation. Recent studies reveal the distinct microRNA expression patterns in T-ALL patients that can serve as diagnostic or prognostic markers. In the present study, we investigated the miRNA and mRNA expression patterns, highlighting their role in modulating disease-associated signalling pathways. Integrative analysis using publicly available miRNA-seq data of pediatric T-ALL patients (E-MTAB-7446, E-MTAB-11987 and GSE89978) was performed to find high-confidence dysregulated miRNA and their target genes using multiple databases (TargetScan, miRDB, miRTarbase). Network study using Cytoscape identified key genes BCL2 , CCND , PTEN , SIRT1 , GSK3B , IL6 , NFKB1 and SMAD4 playing significant roles in key oncogenic pathways like PI3K-Akt signaling pathway and cellular senescence. Final integration with our patient transcriptomic data revealed negatively correlated miRNA-mRNA pairs such as IL6 -hsa-miR-9-5p, FOXO1 -hsa-miR-153-3p, hsa-miR-296-3p- STAT5A , miR-205-5p- FOXM1 , and CENPF . Functional analysis of these pairs revealed these antagonist pairs to be involved in dysregulated IL6/JAK-STAT pathway, TGFβ signaling, and cellular senescence under T-cell leukemic conditions. In conclusion, findings from our study provide important insights regarding the involvement of miRNAs in the T-ALL disease molecular mechanisms, which can serve as biomarker for future intervention.