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.
