BACKGROUND
Thymoma is the most common
tumor of the anterior mediastinum, and can be caused by infrequent
malignancies arising from the epithelial cells of the thymus. Unfortunately, blood-based diagnostic markers are not currently available. High-throughput sequencing technologies, such as
RNA-seq with next-generation sequencing, have facilitated the detection and characterization of both coding and non-coding RNAs (ncRNAs), which play significant roles in genomic regulation, transcriptional and post-transcriptional regulation, and imprinting and epigenetic modification. The knowledge about fusion genes and ncRNAs in
thymomas is scarce. MATERIAL AND METHODS For this study, we gathered large-scale
RNA-seq data belonging to samples from 25
thymomas and 25 healthy thymus specimens and analyzed them to identify fusion genes, lncRNAs, and
miRNAs. RESULTS We found 21 fusion genes, including KMT2A-MAML2, HADHB-REEP1, COQ3-CGA, MCM4-SNTB1, and IFT140-ACTN4, as the most frequent and significant in
thymomas. We also detected 65 differentially-expressed lncRNAs in
thymomas, including AFAP1-AS1, LINC00324, ADAMTS9-AS1, VLDLR-AS1, LINC00968, and NEAT1, that have been validated with the TCGA database. Moreover, we identified 1695
miRNAs from small
RNA-seq data that were overexpressed in
thymomas. Our network analysis of the
lncRNA-
mRNA-
miRNA regulation axes identified a cluster of
miRNAs upregulated in
thymomas, that can trigger the expression of target
protein-coding genes, and lead to the disruption of several biological pathways, including the PI3K-Akt signaling pathway, FoxO signaling pathway, and HIF-1 signaling pathway. CONCLUSIONS Our results show that overexpression of this
miRNA cluster activates PI3K-Akt, FoxO, HIF-1, and Rap-1 signaling pathways, suggesting pathway inhibitors may be therapeutic candidates against
thymoma.