Yu Shanshan, Liang Jinxiao, Liu Lixiao, Chen Ming, Chen Cheng, Zhou Donghui
Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China.
Department of Obstetrics and Gynecology, Ningbo City First Hospital, Ningbo University, Ningbo, China.
J Transl Med. 2025 Mar 6;23(1):290. doi: 10.1186/s12967-025-06287-8.
Gastric cancer (GC) is one of the most common malignancies. Previous studies have shown that mitochondrial metabolism is associated with malignancies. However, relevant research on mitochondria-related lncRNAs in GC is lacking.
We integrated the corresponding information of patients with GC from The Cancer Genome Atlas (TCGA) database. Mitochondria-related lncRNAs were selected based on differential expression and a correlation analysis to construct a prognostic model. The mutation data were analyzed to distinguish differences in the tumor mutation burden (TMB). Single-sample gene set enrichment analysis (ssGSEA) was performed to evaluate immunological differences. A series of cell-based experiments were adopted to evaluate the biological behavior of GC.
A total of 1571 mitochondria-related lncRNAs were identified. A prognostic signature incorporating nine lncRNAs was built based on 293 suitable GC cases and could predict patient prognosis. The TMB and ssGSEA indicated that the low-risk group displayed increased immune function. The enrichment analysis indicated that the differentially expressed genes were enriched in metabolic functions. AC129507.1 was significantly upregulated in GC cells and associated with a poor prognosis, and its knockdown inhibited the proliferation and migration of GC cells. Mechanistically, silencing AC129507.1 led to abnormal glycolipid metabolism and oxidative stress, thus inducing ferroptosis.
Our nine-lncRNA risk signature could powerfully predict patient prognosis. AC129507.1 promoted the malignant phenotypes of GC cells. AC129507.1 could play a nonnegligible role in GC by promoting the formation of a immunosuppressive tumor microenvironment by inhibiting the initiation of ferroptosis, which needs to be further explored.
胃癌（GC）是最常见的恶性肿瘤之一。先前的研究表明，线粒体代谢与恶性肿瘤有关。然而，关于GC中线粒体相关长链非编码RNA（lncRNA）的相关研究尚缺乏。
我们整合了来自癌症基因组图谱（TCGA）数据库的GC患者的相应信息。基于差异表达和相关性分析选择线粒体相关lncRNA，以构建预后模型。分析突变数据以区分肿瘤突变负荷（TMB）的差异。进行单样本基因集富集分析（ssGSEA）以评估免疫差异。采用一系列基于细胞的实验来评估GC的生物学行为。
共鉴定出1571个线粒体相关lncRNA。基于293例合适的GC病例构建了包含9个lncRNA的预后特征，并可预测患者预后。TMB和ssGSEA表明低风险组的免疫功能增强。富集分析表明差异表达基因富集于代谢功能。AC129507.1在GC细胞中显著上调且与预后不良相关，其敲低抑制了GC细胞的增殖和迁移。机制上，沉默AC129507.1导致糖脂代谢和氧化应激异常，从而诱导铁死亡。
我们的九lncRNA风险特征能够有力地预测患者预后。AC129507.1促进了GC细胞的恶性表型。AC129507.1可能通过抑制铁死亡的起始促进免疫抑制性肿瘤微环境的形成，从而在GC中发挥不可忽视的作用，这需要进一步探索。
