Abstract
Gene expression profiling studies have shown the pathogenetic role of oncogenic pathways in extranodal natural killer/T-cell lymphoma (ENKL). In this study, we aimed to identify the microRNAs (miRNAs) playing potential roles in ENKL, and to evaluate the genes and biological pathways associated to them. Gene expression profiles of ENKL patients were acquired from the gene expression omnibus (GEO) database. Most differentially expressed (DE)-miRNAs were identified in ENKL patients using limma package. Gene targets of the DE-miRNAs were collected from online databases (miRDB, miRWalk, miRDIP, and TargetScan), and used in Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses on Database for annotation, visualization, and integrated discovery database, and then used in protein–protein interaction (PPI) analysis on STRING database. Hub genes of the PPI network were identified in cytoHubba, and were evaluated in Biological networks gene ontology. According to the series GSE31377 and GSE43958 from GEO database, four DE-miRNAs were screened out: hsa-miR-363-3p, hsa-miR-296-5p, hsa-miR-155-5p, and hsa-miR-221-3p. Totally 164 gene targets were collected from the online databases, and used in the GO and KEGG pathway analyses and PPI network analysis. Ten hub genes of the PPI network were identified: AURKA, TP53, CDK1, CDK2, CCNB1, PLK1, CUL1, ESR1, CDC20, and PIK3CA. Those hub genes, as well as their correlative pathways, may be of diagnostic or therapeutic potential for ENKL, but further clinical evidence is still expected.
Highlights
Natural killer (NK) cell tumors are categorized as extranodal NK/T-cell lymphoma (ENKL), aggressive NK-cell leukemia, chronic NK-cell lymphoproliferative disorders, etc., according to the 2016 World Health Organization (WHO) classification [1,2]
ENKL is associated with Epstein–Barr virus (EBV) because EBV can infect T and NK cells and lead to EBV-associated T/NK cell lymphoproliferative disorders [1], according to observations of EBV molecules in tumor tissue and the correlations between EBV load and disease diagnosis and prognosis [4]
As lymphoma’s biological behavior is more inclined to solid tumor [40], and we found focal adhesion to play an important role in ENKL, so Focal adhesion kinase (FAK) may serve as an effective therapeutic target to ENKL
Summary
Natural killer (NK) cell tumors are categorized as extranodal NK/T-cell lymphoma (ENKL), aggressive NK-cell leukemia, chronic NK-cell lymphoproliferative disorders, etc., according to the 2016 World Health Organization (WHO) classification [1,2]. ENKL is a unique clinical entity characterized by an aggressive clinical course, and the prognosis is poor [5]. The pathogenesis of this tumor is poorly understood, but in recent years gene expression profiling studies have demonstrated the pathogenetic role of several oncogenic pathways in ENKL, such as AKT, STAT3, NF-KB, Notch-1, and Aurora kinase A [6,7]. In this sense, an important task is to find novel molecular and biological candidates for diagnostic, predictive, and prognostic potential in ENKL, including microRNAs (miRNAs)
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