Identification of Missense SNP of PKC ZETA Associated in HCV Induced Hepatocellular Carcinoma

Abstract

Cancer refers to uncontrolled division of abnormal cells and their ability to transfer to sites other than the origin. Hepatocellular carcinoma is second leading cause of death which arise from uncontrolled division of abnormal cells in liver that can spread to other parts of body. Viral induced carcinoma is widespread, and HCV is one of the potent risk factors in HCC. Single nucleotide polymorphism is widespread phenomenon resulting into mutation in single nucleotide which leads to genetic changes. There is well established fact that genetics are also involved in the occurrence of HCC so analysis of various mutations can lead to good diagnostic and prognostic marker. Protein kinase C is homologous family of protein involved in various cellular functions. Among 3 types of PKC being novel conventional and atypical PKCZ belongs to atypical PKC. This research focuses on the implication of PKCZ gene polymorphism by determining the association of PKCZ (G/A) mutation with liver cancer in Pakistan and conducting an expression analysis of the polymorphic gene. Samples were collected from liver cancer patients, followed by DNA extraction and PCR to analyze the allelic and genotypic frequency, followed by RT PCR for the expression analysis. This study also focuses on in-silico structural and functional analysis of mutant protein via HOPE an I-Mutant. The results of in vivo and in silico analysis were aligned with the fact that the heterozygous mutation in PKCZ is involved in inducing HCC. Whereas the homozygous mutation is more prone to HCV induced HCC. Molecular docking of antioncogenic molecule known as cangoronine was done which can be validated by further studies through wet lab.