SETD8通过抑制RRAD的表达来抑制胰腺癌中的铁死亡。

SETD8 inhibits ferroptosis in pancreatic cancer by inhibiting the expression of RRAD.

作者信息

Lu Zekun, Hu Qiangsheng, Qin Yi, Yang Hao, Xiao Bingkai, Chen Weibo, Ji Shunrong, Zu Guangchen, Wang Zhiliang, Fan Guixiong, Xu Xiaowu, Chen Xuemin

机构信息

Department of Hepatopancreatobiliary Surgery, the Third Affiliated Hospital of Soochow University, Changzhou, 213000, China.

Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China.

出版信息

Cancer Cell Int. 2023 Mar 18;23(1):50. doi: 10.1186/s12935-023-02899-6.

DOI:10.1186/s12935-023-02899-6

PMID:36934248

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10024404/

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

背景

作为一种癌基因，SETD8可促进肿瘤生长和肿瘤细胞增殖。本研究旨在揭示SETD8与胰腺癌铁死亡之间的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。

方法

通过RNA测序分析筛选下游靶点。蛋白质印迹法、实时定量聚合酶链反应（qPCR）和免疫组织化学法显示基因之间的关系。细胞增殖分析和细胞代谢物分析揭示基因的功能。采用染色质免疫沉淀（CHIP）试验研究分子机制。

结果

通过RNA测序分析筛选出SETD8的潜在下游靶点RRAD。通过蛋白质印迹法、实时定量聚合酶链反应（qPCR）和免疫组织化学法发现SETD8与RRAD呈负相关。通过细胞增殖分析和细胞代谢物分析发现，RRAD不仅能抑制癌细胞增殖，还能提高癌细胞脂质过氧化水平。同时，采用染色质免疫沉淀分析（CHIP）探讨SETD8调控RRAD表达的分子机制。SETD8抑制RRAD表达。