Investigating the pathogenic potential of PKC-eta UTR variants in cancer progression

Abstract

A single-nucleotide polymorphism (SNP) is a naturally occurring variation in genomic DNA. Untranslated regions (UTRs) are involved in the regulatory pathways of cells that influence transcriptional and translational mechanisms. PRKCH belongs to the Protein Kinase C (PKC) family, which regulates crucial cellular processes. Limited studies have explored the regulatory and functional impact of UTR variants of PRKCH through in silico and genotyping analysis.,which was the focus of the current study. Pathogenic potential of UTR variants was critically analyzed. Meanwhile, among the 3′UTR variants, the only variant rs14095 (A/G) was ranked as 1f by RegulomeDB and showed a allelic frequency in African populations. This variant also interacted with miRNA “hsa-miR-6074”, which has been reported to regulate “TRP channels” through the KEGG pathway. The 5′UTR variants, including rs114416617 G/A, rs145795985 G/A, rs1951964 C/G, and rs45582331 C/G showed allelic frequency in different populations along with their expression in various organs. Motifs were detected in these 4 variants of 5′UTR region. These variants exhibited a strong chromatin profile. hsa-miR-6074 was reported to regulate p53 signaling, melanoma, FoxO signaling, glioma, MAPK, IL-17, PD-L1, HIF1A, TRAF6, PTEN, carbon metabolism, autophagy, and cellular senescence related pathways. According to genotyping analysis, the mutated genotype (GG) of the 3′ UTR variant rs14095 was significantly associated with Hepatocellular Carcinoma (HCC) risk. In comparison, for the 5′ UTR variant, rs44582331, no significant association was observed between the mutated genotype (TT) and HCC. Furthermore, functional assays need to be carried out to experimentally validate the role of these UTR variants in cancer pathogenesis.