Transcriptome of plasma exosome identifies a hsa-miR-483-5p/mRNAs network that regulates chemotherapy resistance in locally advanced rectal cancer

Abstract

Abstract Chemoresistance is a primary contributor to distant metastasis in the context of neoadjuvant chemoradiotherapy (nCRT) in rectal cancer, the underlying mechanisms remain elusive. In this study, the profiles of plasma exosome miRNAs were compared in two dimensions according to treatment responses (poor/well-responders) and treatment courses (pre/post-nCRT) by RNA-sequencing. The exosome hsa-miR-483-5p was up-regulated in well-responders post-nCRT. The bioinformatic analysis revealed that the target genes of hsa-miR-483-5p were mainly enriched in tumor-specific pathways, like MAPK signaling pathway, EGFR tyrosine kinase inhibitor resistance, Toll-like receptor signaling pathway, VEGF signaling pathway, and mTOR signaling pathway. A further analysis indicated that the genes MAPK3, RAX2, RNF165 were associated with inferior recurrence-free survival in rectal cancer patients, and the profiles of MAPK3, TSPYL5, ZNF417 were correlated with tumor stages. In addition, the expression profiles of MAPK3, RNF165, ZNF417 were negatively correlated with inhibitory concentration 50 values. Accordingly, a network of hsa-miR-483-5p/MAPK3/RNF 165/ZNF417 were constructed. The study provides insights into the mechanism of chemoresistance in terms of exosome miRNAs, but further research is needed within the framework of our established miRNA-mRNA network.