蛋白激酶C-ε（PKCε）是新颖亚家族蛋白激酶C（nPKCs）中的一个成员，对于癌症的发展起着一定作用。研究发现，其表达水平的升高与宫颈癌相关。先前，我们通过多种生物信息学工具和分子动力学模拟，鉴定了其不同结构域的致病性变异。本研究旨在寻找其变异体rs1553369874和rs1345511001与宫颈癌的关联，并确定这些变异体对PKCε蛋白相互作用的影响，从而可能导致癌症的发展和存活率不佳。通过基因分型分析确定了这些变异体与宫颈癌及其临床病理特征的关联。计算了变异体的比值比和相对风险，并使用Fisher确切检验评估了变异体的重要性和疾病风险。进行了蛋白质相互作用对接，并对对接的复合物进行了分子动力学模拟，以评估变异体对PKCε的分子相互作用的影响。这项研究发现，基因变异体rs1553369874和rs1345511001与宫颈癌相关。Smad3与PKCε相互作用，并促进宫颈癌血管生成。因此，选择Smad3进行蛋白质相互作用对接。分析结果显示，PKCε变异体促进与Smad3的异常相互作用，可能导致致癌途径的激活。本研究获得的数据表明PRKCE基因变异体rs1553369874和rs1345511001的预后重要性。通过进一步的体外和体内验证，这些变异体可以作为宫颈癌的新的预后标志物和治疗靶点在临床层面上使用。© 2023年。BioMed Central Ltd.，施普林格自然出版集团的一部分。

Protein Kinase C-epsilon (PKCε) is a member of the novel subfamily of PKCs (nPKCs) that plays a role in cancer development. Studies have revealed that its elevated expression levels are associated with cervical cancer. Previously, we identified pathogenic variations in its different domains through various bioinformatics tools and molecular dynamic simulation. In the present study, the aim was to find the association of its variants rs1553369874 and rs1345511001 with cervical cancer and to determine the influence of these variants on the protein-protein interactions of PKCε, which can lead towards cancer development and poor survival rates.The association of the variants with cervical cancer and its clinicopathological features was determined through genotyping analysis. Odds ratio and relative risk along with Fisher exact test were calculated to evaluate variants significance and disease risk. Protein-protein docking was performed and docked complexes were subjected to molecular dynamics simulation to gauge the variants impact on PKCε's molecular interactions.This study revealed that genetic variants rs1553369874 and rs1345511001 were associated with cervical cancer. Smad3 interacts with PKCε and this interaction promotes cervical cancer angiogenesis; therefore, Smad3 was selected for protein-protein docking. The analysis revealed PKCε variants promoted aberrant interactions with Smad3 that might lead to the activation of oncogenic pathways. The data obtained from this study suggested the prognostic significance of PRKCE gene variants rs1553369874 and rs1345511001.Through further in vitro and in vivo validation, these variants can be used at the clinical level as novel prognostic markers and therapeutic targets against cervical cancer.© 2023. BioMed Central Ltd., part of Springer Nature.