Genetic Variants at PRKCG Splice and UTR Sites Promote Cancer Susceptibility by Disrupting Epigenetic and miRNA Regulatory Network.

The changes in the protein kinase C gamma gene (PRKCG) expression are associated with both coding and non-coding variants. No studies have specifically established the association between PRKCG 3'UTR, 5'UTR, donor and acceptor splice variants with post-transcriptional changes through utilizing tools. The current study intends to uncover this linkage. In total, 419 3' and 5'UTR variants were retrieved. 325 of these variant IDs were annotated as functionally significant. 18 variants impacted the transcription factors binding and therefore influenced the post-transcriptional regulatory activity while 7 variants affected regulatory mechanisms through histone modifications. 2 rsIDs (rs373228, rs446795) potentially impacted the interactions with RNA binding proteins. In addition to that, PRKCG showed high expression in brain cells and had variable expression in TCGA tumors, respectively. Furthermore, 5 3' UTR variants were identified to be targeted by miRNAs. In total, 5 of these miRNAs (hsa-miR-663a, hsa-miR-324-5p, hsa-miR-646, hsa-miR-1205 and hsa-miR-4270) that targeted 3'UTRs (rs57483118, rs181418157 and rs60891969) showed differential expressions in distinct cancer types. The presence of 3'UTR variants likely altered the secondary structure of mRNA. The 7 rsIDs at 3' UTR site caused the loss of function of authentic splice site at 10 positions was noted; at 1 position, gain of function was observed while at 2 positions no effect was identified. Moreover, the loss of donor and acceptor splice site was evident. Our results highlight the importance of non-coding regions that might boost our research capacity to predict and construct targeted therapeutic approaches.