Nandan Parmar Keshri, Sivaraman Jayanthi
School of Biosciences and Technology, Vellore Institute of Technology, Vellore, India.
Discov Oncol. 2025 Jun 7;16(1):1029. doi: 10.1007/s12672-025-02783-x.
Cancer, one of the most dreadful diseases of the twenty-first century develops as a result of unregulated inflammatory responses and mutations of genes. In human cancers, among various mutated genes, the Ras gene is one of the most commonly mutated oncogenes. However, when it comes to inflammation, oncogenic Ras mutants can induce tumorigenesis without tumour suppression loss driven by inflammatory responses. Ras protein is a membrane-bound protein with inbuilt GTPase activity which is activated by a variety of extracellular stimuli, converting from an inactive form to an active form. Oncogenic Ras mutants is continuously activated in cancer, thereby enhancing aberrant downstream signalling that leads to tumorigenesis. So, to highlight the significance of Ras protein in cancer and inflammation, this review discussed the signalling pathway for the activation of Ras protein, the role of Ras in immunity and inflammation, downstream regulators of Ras protein and their inhibitors epigenetic regulation of Ras protein. Moreover, we have also done a database-based search using the Database of Cancer Mutant Protein Domains (DCMP) to find out the single nucleotide polymorphism (SNP) level of the Ras gene in different types of cancer. In terms of future perspective, this review discussed emerging strategies to target Ras protein.
癌症是21世纪最可怕的疾病之一，它是由不受控制的炎症反应和基因突变引起的。在人类癌症中，在各种突变基因中，Ras基因是最常发生突变的致癌基因之一。然而，说到炎症，致癌性Ras突变体可以在不依赖炎症反应导致的肿瘤抑制丧失的情况下诱导肿瘤发生。Ras蛋白是一种具有内在GTPase活性的膜结合蛋白，它被多种细胞外刺激激活，从无活性形式转变为活性形式。致癌性Ras突变体在癌症中持续被激活，从而增强导致肿瘤发生的异常下游信号传导。因此，为了突出Ras蛋白在癌症和炎症中的重要性，本综述讨论了Ras蛋白激活的信号通路、Ras在免疫和炎症中的作用、Ras蛋白的下游调节因子及其抑制剂、Ras蛋白的表观遗传调控。此外，我们还使用癌症突变蛋白结构域数据库（DCMP）进行了基于数据库的搜索，以找出不同类型癌症中Ras基因的单核苷酸多态性（SNP）水平。从未来展望的角度来看，本综述讨论了靶向Ras蛋白的新兴策略。
