Details of siRNA sequences.

Mitochondria are essential organelles involved in cell metabolism and are closely linked to various metabolic disorders. In this study, we aimed to develop a prognostic model for endometrial cancer (EC) patients based on mitochondria-related genes (MRGs), and to investigate the role of MACC1 in EC. As shown in the graphic summary, we retrieved gene expression and clinical data from open-access databases. To construct a predictive signature, we applied the Lasso Cox regression algorithm to MRGs. The predictive performance, immune features, and anti-tumor response of the mitochondrial signature were evaluated through multiple algorithms. Additionally, expression levels of key genes were validated using quantitative Real-Time PCR and Western Blot. A total of 2030 MRGs were retrieved, and 267 were found to be prognostically relevant. Eight MRGs—MACC1, CMPK2, NDUFAF6, DUSP18, TOMM40L, MT-TP, SAMM50, and MAIP1—were identified to construct a prognostic signature for EC. The MRG signature demonstrated significant associations with drug sensitivity, immune therapy, and immune cell infiltration. Based on comprehensive bioinformatic analysis, MACC1 was identified as the most promising MRG candidate in EC. Systematic experimental validation, including both in vitro and in vivo approaches, demonstrated that MACC1 down-regulation significantly suppressed EC progression, highlighting its potential as a therapeutic target.

线粒体是参与细胞代谢的关键细胞器，与多种代谢紊乱疾病密切相关。本研究旨在基于线粒体相关基因（mitochondria-related genes, MRGs）构建子宫内膜癌（endometrial cancer, EC）患者的预后模型，并探究MACC1在子宫内膜癌中的作用。如本研究的图形摘要所示，我们从公开可访问的数据库中获取了基因表达与临床数据。为构建预测特征集，我们针对线粒体相关基因应用了Lasso Cox回归算法。我们通过多种算法评估了该线粒体特征集的预测性能、免疫特征及抗肿瘤应答水平。此外，我们采用实时定量聚合酶链反应（quantitative Real-Time PCR）与蛋白质印迹（Western Blot）对关键基因的表达水平进行了验证。本次研究共检索到2030个线粒体相关基因，其中267个被证实与预后相关。最终筛选出8个线粒体相关基因（MACC1、CMPK2、NDUFAF6、DUSP18、TOMM40L、MT-TP、SAMM50及MAIP1）用于构建子宫内膜癌的预后特征集。该线粒体相关基因特征集与药物敏感性、免疫治疗及免疫细胞浸润均存在显著关联。通过全面的生物信息学分析，MACC1被鉴定为子宫内膜癌中最具潜力的线粒体相关基因候选靶点。我们通过包含体外（in vitro）与体内（in vivo）实验在内的系统性实验验证，证实下调MACC1的表达可显著抑制子宫内膜癌的进展，凸显了其作为治疗靶点的潜在价值。