作为一个致癌基因，SETD8可以促进肿瘤生长和细胞增殖。本研究旨在揭示SETD8与胰腺癌中的铁死亡关系及其在胰腺癌中的作用，为胰腺癌的综合治疗提供可能的新方向。通过RNA测序分析筛选下游靶点，并通过蛋白印迹、实时定量PCR和免疫组化等技术展示基因之间的关系。细胞增殖分析和细胞代谢物分析揭示了基因的功能。使用染色质免疫沉淀（CHIP）实验研究了分子机制。RNA测序分析筛选出SETD8的潜在下游靶点RRAD。通过蛋白印迹、实时定量PCR和免疫组化等技术发现SETD8与RRAD存在负相关。通过细胞增殖分析和细胞代谢物分析发现，RRAD不仅可以抑制癌细胞的增殖，还可以提高癌细胞的脂质过氧化水平。同时，使用染色质免疫沉淀分析（CHIP）探索了SETD8调节RRAD表达的分子机制。SETD8抑制RRAD表达。SETD8与RRAD启动子区域相互作用，表观遗传地沉默RRAD的表达，降低胰腺癌细胞的脂质过氧化水平，从而抑制胰腺癌细胞的铁死亡，导致胰腺癌的预后不良。 ©2023年。作者（们）保留其版权。

As an oncogene, SETD8 can promote tumour growth and tumour cell proliferation. This study aims to reveal the relationship between SETD8 and ferroptosis in pancreatic cancer and its role in pancreatic cancer to provide a possible new direction for the comprehensive treatment of pancreatic cancer.The downstream targets were screened by RNA sequencing analysis. Western blot, Real-time Quantitative PCR (qPCR) and immunohistochemistry showed the relationship between genes. Cell proliferation analysis and cell metabolite analysis revealed the function of genes. Chromatin immunoprecipitation (CHIP) assays were used to study the molecular mechanism.The potential downstream target of SETD8, RRAD, was screened by RNA sequencing analysis. A negative correlation between SETD8 and RRAD was found by protein imprinting, Real-time Quantitative PCR (qPCR) and immunohistochemistry. Through cell proliferation analysis and cell metabolite analysis, it was found that RRAD can not only inhibit the proliferation of cancer cells but also improve the level of lipid peroxidation of cancer cells. At the same time, chromatin immunoprecipitation analysis (CHIP) was used to explore the molecular mechanism by which SETD8 regulates RRAD expression. SETD8 inhibited RRAD expression.SETD8 interacts with the promoter region of RRAD, which epigenetically silences the expression of RRAD to reduce the level of lipid peroxidation in pancreatic cancer cells, thereby inhibiting ferroptosis in pancreatic cancer cells and resulting in poor prognosis of pancreatic cancer.© 2023. The Author(s).