Key Laboratory for Translational Research and Innovative Therapeutics of Gastrointestinal Oncology, Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of General Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Sci Rep. 2024 Aug 13;14(1):18757. doi: 10.1038/s41598-024-69789-3.
Hepatocellular carcinoma (HCC) still presents poor prognosis with low overall survival rates and limited therapeutic options available. Recently, attention has been drawn to peptidomic analysis, an emerging field of proteomics for the exploration of new potential peptide drugs for the treatment of various diseases. However, research on the potential function of HCC peptides is lacking. Here, we analyzed the peptide spectrum in HCC tissues using peptidomic techniques and explored the potentially beneficial peptides involved in HCC. Changes in peptide profiles in HCC were examined using liquid chromatography-mass spectrometry (LC-MS/MS). Analyze the physicochemical properties and function of differently expressed peptides using bioinformatics. The effect of candidate functional peptides on HCC cell growth and migration was evaluated using the CCK-8, colony formation, and transwell assays. Transcriptome sequencing analysis and western blot were employed to delve into the mode of action of potential peptide on HCC. Peptidomic analysis of HCC tissue yielded a total of 8683 peptides, of which 452 exhibited up-regulation and 362 showed down-regulation. The peptides that were differentially expressed, according to bioinformatic analysis, were closely linked to carbon metabolism and the mitochondrial inner membrane. The peptide functional validation identified a novel peptide, PDLC (peptide derived from liver cancer), which was found to dramatically boost HCC cell proliferation through the Ras/Raf/MEK/ERK signaling cascade. Our research defined the peptide's properties and pattern of expression in HCC and identified a novel peptide, PDLC, with a function in encouraging HCC progression, offering an entirely new potential therapeutic target the disease.
肝细胞癌（HCC）的总体生存率仍然较低，预后较差，治疗选择有限。最近，人们对肽组学分析引起了关注，肽组学是蛋白质组学的一个新兴领域，用于探索治疗各种疾病的新的潜在肽类药物。然而，对于 HCC 肽的潜在功能的研究还很缺乏。在这里，我们使用肽组学技术分析了 HCC 组织中的肽谱，并探索了可能参与 HCC 的潜在有益肽。使用液相色谱-质谱联用（LC-MS/MS）检测 HCC 中肽谱的变化。使用生物信息学分析不同表达肽的理化性质和功能。使用 CCK-8、集落形成和 Transwell 测定评估候选功能肽对 HCC 细胞生长和迁移的影响。通过转录组测序分析和 Western blot 深入研究潜在肽对 HCC 的作用机制。对 HCC 组织的肽组学分析共产生了 8683 种肽，其中 452 种呈上调表达，362 种呈下调表达。根据生物信息学分析，差异表达的肽与碳代谢和线粒体内膜密切相关。肽功能验证确定了一种新型肽 PDLC（源自肝癌的肽），它通过 Ras/Raf/MEK/ERK 信号通路显著促进 HCC 细胞增殖。我们的研究定义了 HCC 中肽的性质和表达模式，并确定了一种新型肽 PDLC，它具有促进 HCC 进展的功能，为该疾病提供了一个全新的潜在治疗靶点。
