MiRNA profiling in adult T-cell leukemia lymphoma (ATLL), a systems virology study

Abstract

Due to a lack of adequate knowledge regarding the mechanism of action and signaling pathways, Adult T-Cell Lymphoma/Leukemia (ATLL) remained a poor prognostic cancer. Understanding the pathogenesis and signaling pathway can be helpful for introducing the possible treatment for ATLL patients. In this study, differentially expressed microRNAs (DEMs) were detected based on the value of log fold change. The gene targets of miRNAs were extracted using miRDB online tool. Protein-protein interaction networks (PPINs) were reconstructed using STRING database and the sub-networks were then determined based on the network centrality measures. Pathway analysis was performed, and proteins participating in the enriched pathways were selected to propose the HTLV1 implicated signaling network (HISN). Thirty-three DEMs consisted of 31 downregulated and 2 upregulated DEMs were detected. Based on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, the proteins contributing in HISN were involved in processes resulting in proliferation, inflammation, anti-apoptosis effects, differentiation, microtubule organizing center (MTOC) relocation, cellular proliferation, cell cycle progression, inhibition of nucleotide excision repair, accumulation of mutations, cellular transformation, matrix proteolytic degradation, and DNA damages. Overexpression of anti-apoptotic genes, including NRAS, CCND1, and CCND2 or deletion/silencing of proapoptotic genes, including TP53 and CASP3, inactivates the intrinsic apoptotic pathways and may lead to developing ATLL.