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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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景：PRKCG编码PKCγ，它被归类为经典的蛋白激酶C家族。在肝细胞癌（HCC）的背景下，没有研究明确确定PRKCGnsSNP与PKCγ的结构和功能变异之间的关系。本研究旨在通过计算机和实验研究揭示这一联系。
方法：预测PKCγ的三维结构。运行分子动力学(MD)模拟，并对相互作用进行估计，稳定性,野生和突变结构之间的保守性和翻译后变化。确定PRKCG水平与HCC生存率的相关性。进行基因分型分析以调查与HCC的有害PRKCGnsSNP关联。PKCγmRNA表达,HIF-1α,AKT,分析了对照和HCC患者血液中的SOCS3和VEGF，并构建了描述这些相互作用的遗传级联。
结果：将所研究的癌基因的表达水平与肿瘤抑制基因进行比较。通过Alphafold，探索了PKCγ的三维结构。15个SNP被缩小用于在外显子5、10和18以及PKCγ的调节和激酶结构域中鉴定的计算机分析。均方根偏差和随回转半径的波动揭示了野生和突变变体结构之间的潜在变化。突变基因型AA（纯合）对应于nsSNP，rs386134171在OR患者中频率更高(2.446)，RR（1.564）和P值（<0.0029），突出了其与HCC的显着关联，与发现野生基因型GG更为普遍的对照相比。
结论：nsSNPrs386134171可以作为HCC诊断和治疗研究的遗传标记。这项研究为将来在HCC上进行的研究制定了路线图。
方法：预测PKCγ的三维结构。运行分子动力学(MD)模拟，并对相互作用进行估计，稳定性,野生和突变结构之间的保守性和翻译后变化。确定PRKCG水平与HCC生存率的相关性。进行基因分型分析以调查与HCC的有害PRKCGnsSNP关联。PKCγmRNA表达,HIF-1α,AKT,分析了对照和HCC患者血液中的SOCS3和VEGF，并构建了描述这些相互作用的遗传级联。
结果：将所研究的癌基因的表达水平与肿瘤抑制基因进行比较。通过Alphafold，探索了PKCγ的三维结构。15个SNP被缩小用于在外显子5、10和18以及PKCγ的调节和激酶结构域中鉴定的计算机分析。均方根偏差和随回转半径的波动揭示了野生和突变变体结构之间的潜在变化。突变基因型AA（纯合）对应于nsSNP，rs386134171在OR患者中频率更高(2.446)，RR（1.564）和P值（<0.0029），突出了其与HCC的显着关联，与发现野生基因型GG更为普遍的对照相比。
结论：nsSNPrs386134171可以作为HCC诊断和治疗研究的遗传标记。这项研究为将来在HCC上进行的研究制定了路线图。
