Saadh Mohamed J, Ahmed Hanan Hassan, Kareem Radhwan Abdul, Bishoyi Ashok Kumar, Roopashree R, Shit Debasish, Arya Renu, Joshi Kamal Kant, Sameer Hayder Naji, Yaseen Ahmed, Athab Zainab H, Adil Mohaned
Faculty of Pharmacy, Middle East University, Amman 11831, Jordan.
College of Pharmacy, Alnoor University, Mosul, Iraq.
Pathol Res Pract. 2025 May;269:155905. doi: 10.1016/j.prp.2025.155905. Epub 2025 Mar 8.
The tumor microenvironment (TME) plays a crucial role in the development and progression of gastric cancer (GC). The TME comprises a network of cancer cells, immune cells, fibroblasts, endothelial cells, and extracellular matrix components, which provide a supportive niche for cancer cells. This study investigates the role of TME-derived exosomal competitive endogenous RNAs (ceRNAs), particularly long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), as major regulating agents in GC development. Exosomal ceRNAs control gene expression across several TME components, amplifying cancer hallmarks like cell proliferation, invasion, metastases, and chemoresistance. They promote dynamic interplay between cancer cells and adjacent stromal cells, enabling tumor development through immune suppression, angiogenesis, and epithelial-mesenchymal transition (EMT). Exosomal ceRNAs can modify the TME, creating a pro-tumorigenic milieu and preparing cancer cells to avoid immunological responses, defy death, and adapt to therapeutic pressures. This review highlights the understudied interactions between the TME and exosomal ceRNAs in gastric cancer and emphasizes their potential utility as diagnostic and therapeutic tools.
肿瘤微环境（TME）在胃癌（GC）的发生和发展中起着至关重要的作用。肿瘤微环境由癌细胞、免疫细胞、成纤维细胞、内皮细胞和细胞外基质成分组成的网络构成，为癌细胞提供了一个支持性的生态位。本研究调查了肿瘤微环境衍生的外泌体竞争性内源RNA（ceRNA），特别是长链非编码RNA（lncRNA）和环状RNA（circRNA），作为胃癌发展中的主要调节因子的作用。外泌体ceRNA控制着多个肿瘤微环境成分的基因表达，放大了细胞增殖、侵袭、转移和化疗耐药等癌症特征。它们促进癌细胞与相邻基质细胞之间的动态相互作用，通过免疫抑制、血管生成和上皮-间质转化（EMT）实现肿瘤发展。外泌体ceRNA可以改变肿瘤微环境，创造一个促肿瘤的环境，并使癌细胞能够避免免疫反应、抵抗死亡并适应治疗压力。本综述强调了在胃癌中肿瘤微环境与外泌体ceRNA之间尚未充分研究的相互作用，并强调了它们作为诊断和治疗工具的潜在用途。
