代谢重编程是癌症的标志，在精准肿瘤治疗中发挥着关键作用。长非编码 RNA (lncRNA) 调节癌细胞行为，包括代谢。二硫下垂症是一种新发现的由葡萄糖饥饿引发的受调节细胞死亡形式，在结肠腺癌 (COAD) 中尚未得到充分了解。本研究旨在证实COAD中二硫下垂的存在和作用，并鉴定可能靶向诱导COAD中二硫下垂的二硫下垂相关lncRNA。采用PI和F-肌动蛋白染色观察COAD细胞系中二硫下垂的情况。根据 TCGA-COAD 数据库中二硫下垂相关基因的表达，鉴定了二硫下垂相关的 lncRNA。建立了二硫下垂症的四长链非编码RNA特征。随后，功能丧失检测探索了 AC013652.1 和 MCM3AP-AS1 在二硫下垂中的作用。在葡萄糖饥饿下的 COAD 细胞中观察到二硫下垂，并且可以通过防止二硫键应激的药物（例如二硫苏糖醇 (DTT) 和 tris）逆转-(2-羧乙基)-膦(TCEP)。 COAD 患者中二硫下垂相关基因的预后价值得到证实，表达越高表明生存期越长。基于这些基因的表达，建立了包含四个 lncRNA 的二硫下垂相关 lncRNA 特征。其中，AC013652.1和MCM3AP-AS1预测预后较差。此外，抑制 AC013652.1 或 MCM3AP-AS1 会增加二硫下垂相关基因的表达和细胞死亡，这可以通过 DTT 和 TCEP 逆转。这项研究提供了迄今为止未记录的证据，证明二硫下垂的存在以及二硫下垂相关基因的预后价值COAD。重要的是，我们鉴定了 lncRNA AC013652.1 和 MCM3AP-AS1，它们可抑制二硫下垂，并可能作为 COAD 的潜在治疗靶点。© 2024。作者。

Metabolic reprogramming is a hallmark of cancer and plays a key role in precision oncology treatment. Long non-coding RNAs (lncRNAs) regulate cancer cell behavior, including metabolism. Disulfidptosis, a newly identified form of regulated cell death triggered by glucose starvation, has yet to be fully understood in colon adenocarcinoma (COAD). This study aimed to confirm the existence and role of disulfidptosis in COAD and identify disulfidptosis-related lncRNAs that may be targeted to induce disulfidptosis in COAD.PI and F-actin staining were used to observe disulfidptosis in COAD cell lines. Disulfidptosis-related lncRNAs were identified based on the expression of disulfidptosis-associated genes in the TCGA-COAD database. A four-lncRNA signature for disulfidptosis was established. Subsequently, loss-of-function assays explored the roles of AC013652.1 and MCM3AP-AS1 in disulfidptosis.Disulfidptosis was observed in COAD cells under glucose starvation and could be reversed by agents that prevent disulfide stress, such as dithiothreitol (DTT) and tris-(2-carboxyethyl)-phosphine (TCEP). The prognostic value of disulfidptosis-associated genes in COAD patients was confirmed, with higher expression indicating longer survival. A disulfidptosis-related lncRNA signature comprising four lncRNAs was established based on the expression of these genes. Among these, AC013652.1 and MCM3AP-AS1 predicted worse prognoses. Furthermore, inhibiting AC013652.1 or MCM3AP-AS1 increased disulfidptosis-associated gene expression and cellular death, which could be reversed by DTT and TCEP.This study provides hitherto undocumented evidence of the existence of disulfidptosis and the prognostic value of disulfidptosis-associated genes in COAD. Importantly, we identified lncRNAs AC013652.1 and MCM3AP-AS1, which suppress disulfidptosis and may serve as potential therapeutic targets for COAD.© 2024. The Author(s).