Decoding the functional roles of intronic microRNA miR-2355 and its host gene KLF7 in immunobiology of cervical cancer

Abstract

Intronic miRNAs are human miRNA genes that sit within the intronic regions of proteincoding host genes and influence their hosts’ function either antagonistically or synergistically. However, previous research has shown that the co-expression of intronic miRNAs and their related host genes is required to keep the biological system resilient and to elucidate their functional relationship. In this study, through processing the raw gene expression data of the whole transcriptome sequencing in human cervical adenocarcinoma and normal cervical tissues from the GEO database (GSE145372), we identified the deregulated miRs and deregulated genes in cervical cancer patients. Among them we found 22 DE intronic miRNAs along with their associated DE host genes. We selected the DE intronic miRNA hsa-mir-2355 and itsDE transcription factor-encoding host gene KLF7 as they are associated with prognosis in cervical cancer patients. Besides, the selected gene pair play roles in the several immune signaling pathways such as IGF1 pathway, IFN-gamma pathway, TRAIL signaling pathway, and S1P1 pathway etc. Furthermore, we identified a total of 227 common targets of KLF7 and hsa-mir-2355, and among them 25 genes were significantly associated with cervical cancer patient survival. Then to shed insights onto the oncoimmunology, we further selected four genes namely AGT12, KRAS, PRKAR1 and REL that can play synergetic or antagonistic role in the immunology. While searching for the correlation between the expression of these genes with immune infiltration in cervical cancer, we observed that expression of REL has significant association of recruiting CD4+ T-cells in the tumor microenvironment which evidently supports the prevalence of observed CD4+ T-cells amongst the tumor cells in the analyzed expression data of the cervical cancer patients. All these results imply that intronic microRNAs have a regulatory influence on the transcriptor factor encoding host genes, thereby promoting cancer spreading or assisting in tumor destruction in the tumor microenvironment. The result identified through these approaches might be used as potential candidates for cancer diagnosis and therapy.