Yanqi Ying, Jingyan Zhang , Dan Ren, Panpan Zhao, Wenyi Zhang, Xiaoqin Lu
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Using qPCR, Western blot, and Immunohistochemical assays to detect the expression of ERP29, the effect of ERP29 on cancer cell proliferation was investigated through CCK8, EdU and clone formation experiments. M6A modifications were studied using m6A Dot blot and MeRIP-qPCR. Finally, we conducted rescue experiments.</p></div><div><h3>Key findings</h3><p>Ten ERS-related hub genes with m6A were identified. ERP29 is highly expressed in EC. ERP29 knockdown inhibits EC cell proliferation. METTL3 overexpression increases the ERP29 mRNA m6A and decreases the expression of ERP29. Cycloleucine (Cyc), a nucleic acid methylation inhibitor, treatment reduces ERP29 mRNA m6A and increases the expression of ERP29. Cyc rescue the low expression of ERP29 caused by overexpression of METTL3 through m6A. ERP29 knockdown rescued the increased proliferation of EC cells caused by low m6A.</p></div><div><h3>Significance</h3><p>ERP29 is highly expressed in EC. m6A regulates ERP29 expression and affects the proliferation of endometrial cancer cells. This represents the premise for applying ERP29 and m6A modifications in diagnosing and treating EC.</p></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"354 ","pages":"Article 122976"},"PeriodicalIF":5.2000,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"ERP29 regulates the proliferation of endometrial carcinoma via M6A modification\",\"authors\":\"Yanqi Ying, Jingyan Zhang , Dan Ren, Panpan Zhao, Wenyi Zhang, Xiaoqin Lu\",\"doi\":\"10.1016/j.lfs.2024.122976\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Aims</h3><p>Endoplasmic reticulum protein 29 (ERP29) is crucial for endoplasmic reticulum stress (ERS). M6A plays an important role in the progression of endometrial cancer (EC). 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引用次数: 0
摘要
目的：内质网蛋白 29（ERP29）对内质网应激（ERS）至关重要。M6A在子宫内膜癌（EC）的进展过程中起着重要作用。本研究探讨了ERS相关基因（ERP29）和m6A在子宫内膜癌中的作用：我们使用 WGCNA 和两种机器学习算法，基于 GEO 数据集、GSEA 数据集和 TCGA-UCEC 数据库筛选了 ERS 相关基因。m6A 相关的 GEO 数据集用于鉴定与 m6A 相关的 ERS 枢纽基因。通过scRNA-seq数据分析可视化枢纽基因在不同细胞类型中的表达。利用 qPCR、Western 印迹和免疫组化检测ERP29的表达，并通过CCK8、EdU和克隆形成实验研究ERP29对癌细胞增殖的影响。通过m6A点印迹和MeRIP-qPCR研究了M6A修饰。最后，我们进行了挽救实验：发现了 10 个具有 m6A 的 ERS 相关枢纽基因。ERP29在EC中高表达。敲除ERP29可抑制EC细胞增殖。METTL3过表达会增加ERP29 mRNA m6A并降低ERP29的表达。核酸甲基化抑制剂环亮氨酸（Cyc）可降低ERP29 mRNA m6A，增加ERP29的表达。Cyc通过m6A挽救了METTL3过表达引起的ERP29低表达。ERP29敲除可挽救因低m6A导致的EC细胞增殖增加：m6A调节ERP29的表达，影响子宫内膜癌细胞的增殖。这为应用ERP29和m6A修饰诊断和治疗EC提供了前提。
ERP29 regulates the proliferation of endometrial carcinoma via M6A modification
Aims
Endoplasmic reticulum protein 29 (ERP29) is crucial for endoplasmic reticulum stress (ERS). M6A plays an important role in the progression of endometrial cancer (EC). The study investigated the role of ERS-related gene (ERP29) and m6A in EC.
Materials and methods
We screened ERS-related genes based on the GEO dataset, GSEA dataset and TCGA-UCEC database using WGCNA and two machine learning algorithms. The m6A-related GEO dataset was employed to identify the ERS-related hub genes with m6A. Expression of hub genes in different cell types were visualize through scRNA-seq data analyzing. Using qPCR, Western blot, and Immunohistochemical assays to detect the expression of ERP29, the effect of ERP29 on cancer cell proliferation was investigated through CCK8, EdU and clone formation experiments. M6A modifications were studied using m6A Dot blot and MeRIP-qPCR. Finally, we conducted rescue experiments.
Key findings
Ten ERS-related hub genes with m6A were identified. ERP29 is highly expressed in EC. ERP29 knockdown inhibits EC cell proliferation. METTL3 overexpression increases the ERP29 mRNA m6A and decreases the expression of ERP29. Cycloleucine (Cyc), a nucleic acid methylation inhibitor, treatment reduces ERP29 mRNA m6A and increases the expression of ERP29. Cyc rescue the low expression of ERP29 caused by overexpression of METTL3 through m6A. ERP29 knockdown rescued the increased proliferation of EC cells caused by low m6A.
Significance
ERP29 is highly expressed in EC. m6A regulates ERP29 expression and affects the proliferation of endometrial cancer cells. This represents the premise for applying ERP29 and m6A modifications in diagnosing and treating EC.
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