Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China; Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan Province 610041, China.
Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China; Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan Province 610041, China.
Pharmacol Res. 2023 Sep;195:106880. doi: 10.1016/j.phrs.2023.106880. Epub 2023 Aug 3.
Gastrointestinal cancer remains a significant global health burden. The pursuit of advancing the comprehension of tumorigenesis, along with the identification of reliable biomarkers and the development of precise therapeutic strategies, represents imperative objectives in this field. Exosomes, small membranous vesicles released by most cells, commonly carry functional biomolecules, including noncoding RNAs (ncRNAs), which are specifically sorted and encapsulated by exosomes. Exosome-mediated communication involves the release of exosomes from tumor or stromal cells and the uptake by nearby or remote recipient cells. The bioactive cargoes contained within these exosomes exert profound effects on the recipient cells, resulting in significant modifications in the tumor microenvironment (TME) and distinct alterations in gastrointestinal tumor behaviors. Due to the feasibility of isolating exosomes from various bodily fluids, exosomal ncRNAs have shown great potential as liquid biopsy-based indicators for different gastrointestinal cancers, using blood, ascites, saliva, or bile samples. Moreover, exosomes are increasingly recognized as natural delivery vehicles for ncRNA-based therapeutic interventions. In this review, we elucidate the processes of ncRNA-enriched exosome biogenesis and uptake, examine the regulatory and functional roles of exosomal ncRNA-mediated intercellular crosstalk in gastrointestinal TME and tumor behaviors, and explore their potential clinical utility in diagnostics, prognostics, and therapeutics.
胃肠道癌症仍然是一个重大的全球健康负担。推进对肿瘤发生的理解，以及识别可靠的生物标志物和开发精确的治疗策略，是该领域的重要目标。外泌体是大多数细胞释放的小膜囊泡，通常携带功能性生物分子，包括非编码 RNA（ncRNA），这些 RNA 被外泌体特异性分拣和包裹。外泌体介导的通讯涉及肿瘤或基质细胞中外泌体的释放以及附近或远程受体细胞的摄取。这些外泌体中包含的生物活性货物对受体细胞产生深远影响，导致肿瘤微环境（TME）发生显著变化，并显著改变胃肠道肿瘤的行为。由于从各种体液中分离外泌体具有可行性，因此外泌体 ncRNA 作为基于液体活检的不同胃肠道癌症标志物显示出巨大潜力，可使用血液、腹水、唾液或胆汁样本。此外，外泌体越来越被认为是基于 ncRNA 的治疗干预的天然递送载体。在这篇综述中，我们阐述了富含 ncRNA 的外泌体生物发生和摄取的过程，研究了外泌体 ncRNA 介导的细胞间串扰在胃肠道 TME 和肿瘤行为中的调节和功能作用，并探讨了它们在诊断、预后和治疗方面的潜在临床应用。
