The regulation of expression and splicing of transcription factors are related to the muscle damage caused by radiation in tree shrews

Radiotherapy induced muscle injury (RIMI) is a major risk for patients that have received radiotherapy for nasopharyngeal carcinoma. The transcription factor (TF) and alternative splicing are crucial events in transcriptional and posttranscriptional regulation, respectively, and could be involved in the signaling pathways of a variety of human disorders, which include radiation injury. To investigate TFs and alternative splicing events in RIMI, we constructed tree shrew model as described previously in which the RIMI group got 20 Gy of irradiation on Tensor veli palatini (TVP) muscles, and the irradiated muscles were evaluated by RNA sequencing (RNA-seq) 6 months later compared to normal TVP muscles. The alt5p and alt3p events were the two main types of differential alternative splicing events (RASEs) identified via the Splice sites Usage Variation Analysis (SUVA) software, and RASEs presented highly conserved in RIMI. According to functional enrichment analysis, RASEs were shown to be primarily enriched in pathways related to transcriptional regulation. Furthermore, we identified 16 alternative splicing TFs (ASTFs) in ASTFs-DEGs networks based on co-expression analysis and the regulatory networks were chiefly enriched in pathways linked to cell proliferation and differentiation. This study revealed that RASEs and ASTFs-DEGs networks may both play an important regulatory role in genes expression network remodeling of RIMI. Future studies on the targeting mechanisms and early intervention of RASEs and ASTFs-DEGs networks may aid in the treatment of RIMI.