MiRNAs hsa-miR-30a-5p and hsa-miR-99b-5p regulate chemokine-mediated immune response in colorectal cancer.

Abstract

e15500 Background: The immune response plays a key role in the oncogenesis of colorectal cancer. The heterogeneity of the tumor environment determines the need for immunogenetic profiling to identify associations with the implementation of tumor-specific immune responses in colorectal cancer. The purpose of our study was to describe the expression profiles of miRNAs and genes involved in the regulation of the immune response in colorectal cancer. Methods: The study included 18 patients (median age 66 years) diagnosed with colorectal cancer who were treated at the National Medical Research Centre for Oncology in 2018-2019. Total RNA was isolated using TRIzol (Thermo Fisher, USA) followed by treatment with DNase 1 (ThermoFisher, USA). Sequencing of RNA samples was performed using two approaches: AmpliSeq for Illumina Immune Response Panel (Illumina, USA) and TruSeq Small RNA Library Prep Kit -Set A (Illumina, USA) according to the manufacturer's instructions on a NextSeq 550 device (llumina, USA). Results: The study revealed 168 differentially expressed genes and 46 differentially expressed miRNAs (p < 0.05). 29 miRNA-mRNA pairs were identified. It has been established that the key signaling mechanism involved in the regulation of the tumor-specific immune response is chemokine signaling pathway (hsa04062). Expression of the CXCL1 and CXCL10 genes encoding the chemokines of the same name is increased in tumor cells (logFC = 1.51, p = 0.006 and logFC = 2.67, p < 0.001, respectively). At the same time, the level of hsa-miR-30a-5p and hsa-miR-99b-5p, which negatively regulate the expression of CXCL1 and CXCL10, is decreased (logFC = -2.26, p < 0.001 and logFC = -1.57, p < 0.001). Conclusions: Activation of expression CXCL1 and CXCL10 with simultaneous loss of negative regulators hsa-miR-30a-5p and hsa-miR-99b-5p was determined in colorectal tumors by NGS-sequencing, which seems promising for the development of personalized therapy, based on the immunogenetic features of colon tumors.