RESUMO
BACKGROUND: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL) are both severe diseases caused by Human T-lymphotropic virus type 1 (HTLV-1) infection, while about 95% of infected cases remain asymptomatic. Genes that play a role in ATLL development are assumed to be dissimilar from the ones that are crucial factors for HAM/TSP occurrence. OBJECTIVE: The expression of six genes including BRCA1, CHUCK, ESR1, NFKBIA, PIK3R1, and PPARG were assessed in two groups of HAM/TSP and ATLL patients. Materials and Methods: cDNA was synthesized from purified RNA, and RT-qPCR was conducted to assess the expression of the genes in two groups. Any possible correlation among the genes' expression was also calculated. Results: BRCA1 and CHUCK expressions were higher in HAM/TSP patients in comparison with ATLL patients. However, ESR1, NFKBIA, PIK3R1, and PPARG are more expressed in ATLL cases than HAM/TSP. A significant positive correlation was observed between BRCA1 and NFKBIA in HAM/TSP group. In addition, a significant negative correlation between PIK3R1 and PPARG in HAM/TSP and between ESR1 and NFKBIA in the ATLL group was obtained. CONCLUSION: HAM/TSP or ATLL stem from a disturbance in the expression of diverse genes and these dissimilarities should be discovered to reach a better understanding of disease treatment as well as screening and assessing the asymptomatic carriers' condition for developing severe disease.
RESUMO
OBJECTIVES: Human lymphotropic virus type 1 (HTLV-1) is the cause of two major diseases, ATLL and HAM/TSP in a percentage of carriers. Despite progress in understanding the pathogenesis of these two diseases, the exact pathogenesis mechanism is still not well understood. High-throughput technologies have revolutionized medical research. This study aims to investigate the mechanism of pathogenesis of these two diseases using the results of high-throughput analysis of microarray datasets. RESULTS: A total of 100 differentially expressed genes were found between ATLL and HAM/TSP. After constructing protein-protein network and further analyzing, proteins including ATM, CD8, CXCR4, PIK3R1 and CD2 were found as the hub ones between ATLL and HAM/TSP. Finding the modules of the subnetwork revealed the enrichment of two common pathways including FOXO signaling pathway and Cell cycle with two common genes including ATM and CDKN2D. Unlike ATLL, ATM gene had higher expressions in HAM/TSP patients. The expression of CDKN2D was increased in ATLL patients. The results of this study could be helpful for understanding the pathogenic mechanism of these two diseases in the same signaling pathways.
Assuntos
Vírus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T do Adulto , Paraparesia Espástica Tropical , Humanos , Paraparesia Espástica Tropical/patologia , Leucemia-Linfoma de Células T do Adulto/patologia , Análise em Microsséries , Transdução de Sinais/genéticaRESUMO
OBJECTIVES: Human T cell leukemia virus-1 (HTLV-1) infection may lead to one or both diseases including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) or adult T cell leukemia lymphoma (ATLL). The complete interactions of the virus with host cells in both diseases is yet to be determined. This study aims to construct an interaction network for distinct signaling pathways in these diseases based on finding differentially expressed genes (DEGs) between HAM/TSP and ATLL. RESULTS: We identified 57 hub genes with higher criteria scores in the primary protein-protein interaction network (PPIN). The ontology-based enrichment analysis revealed following important terms: positive regulation of transcription from RNA polymerase II promoter, positive regulation of transcription from RNA polymerase II promoter involved in meiotic cell cycle and positive regulation of transcription from RNA polymerase II promoter by histone modification. The upregulated genes TNF, PIK3R1, HGF, NFKBIA, CTNNB1, ESR1, SMAD2, PPARG and downregulated genes VEGFA, TLR2, STAT3, TLR4, TP53, CHUK, SERPINE1, CREB1 and BRCA1 were commonly observed in all the three enriched terms in HAM/TSP vs. ATLL. The constructed interaction network was then visualized inside a mirrored map of signaling pathways for ATLL and HAM/TSP, so that the functions of hub genes were specified in both diseases.