Non-synonymous SNPs variants of PRKCG and its association with oncogenes predispose to hepatocellular carcinoma

Abstract

Background PRKCG encodes PKC γ, which is categorized under the classical protein kinase C family. No studies have specifically established the relationship between PRKCG nsSNPs with structural and functional variations in PKC γ in the context of hepatocellular carcinoma (HCC). The present study aims to uncover this link through in-silico and experimental studies. Methods The 3D structure of PKC γ was predicted. Molecular Dynamic (MD) Simulations were run and estimates were made for interactions, stability, conservation and post-translational alterations between wild and mutant structures. The association of PRKCG levels with HCC survival rate was determined. Genotyping analyses were conducted to investigate the deleterious PRKCG nsSNP association with HCC. mRNA expression of PKC γ, HIF-1 alpha, AKT, SOCS3 and VEGF in the blood of controls and HCC patients was analyzed and a genetic cascade was constructed depicting these interactions. Results The expression level of studied oncogenes was compared to tumour suppressor genes. Through Alphafold, the 3D structure of PKC γ was explored. Fifteen SNPs were narrowed down for in-silico analyses that were identified in exons 5, 10 and 18 and the regulatory and kinase domain of PKC γ. Root mean square deviation and fluctuation along with the radius of gyration unveiled potential changes between the wild and mutated variant structures. Mutant genotype AA (homozygous) corresponding to nsSNP, rs386134171 had more frequency in patients with OR (2.446), RR (1.564) and P-values (< 0.0029) that highlights its significant association with HCC compared to controls in which the wild genotype GG was found more prevalent. Conclusion nsSNP rs386134171 can be a genetic marker for HCC diagnosis and therapeutic studies. This study has laid down a road map for future studies to be conducted on HCC.

Alcohol Intubation and Synergistic Effect of Folic Acid and Egg Yolk Powder Solution on Alcohol Dehydrogenase [ADH] Class I Gene Expression and Single Nucleotide Polymorphism Frequency in Parent and Prenatal Alcohol Exposed Wistar Rats

“…Variation in metabolism rate, compulsive alcohol use, altered behavior, and deleterious effects has been attributed to Single Nucleotide Polymorphisms (SNPs) occurrence in alcohol metabolizing genes in PAE fetuses and alcohol users (Ong et al, 2018;Katsarou et al, 2017). Non-synonymous SNPs (nsSNPs) comprise a group of SNPs that, together with SNPs in regulatory regions, are believed to have the highest impact on phenotype (Abid et al, 2023;Robert and Pelletier, 2018). Based on gene expression and sequence alignment, there are seven distinct genes relating to the five enzyme classes namely: Class 1-ADH1A (MIM %103700), ADH1B and ADH1C; class II, ADH4 (MIM % 103740); class III, ADH5 (MIM %103710); class IV, ADH7 (MIM %600086); and class V, ADH6 (MIM %103735) (Osier et al, 2002).…”