Department of Gastroenterology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Digestive Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China.
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Dental Maxillofacial Reconstruction and Biological Intelligence Manufacturing, School of Stomatology, Lanzhou University, Lanzhou 730030, China.
Pharmacol Res. 2024 Jul;205:107216. doi: 10.1016/j.phrs.2024.107216. Epub 2024 May 16.
Gastric cancer (GC) is the leading cause of cancer-related death worldwide, and it is associated with a combination of genetic, environmental, and microbial risk factors. Helicobacter pylori (H. pylori) is classified as a type I carcinogen, however, the exact regulatory mechanisms underlying H. pylori-induced GC are incompletely defined. MicroRNAs (miRNAs), one of small non-coding RNAs, negatively regulate gene expression through binding to their target genes. Dysregulation of miRNAs is crucial in human cancer. A noteworthy quantity of aberrant miRNAs induced by H. pylori through complex regulatory networks have been identified. These miRNAs substantially affect genetic instability, cell proliferation, apoptosis, invasion, metastasis, autophagy, chemoresistance, and the tumor microenvironment, leading to GC development and progression. Importantly, some H. pylori-associated miRNAs hold promise as therapeutic tools and biomarkers for GC prevention, diagnosis, and prognosis. Nonetheless, clinical application of miRNAs remains in its infancy with multiple issues, including sensitivity and specificity, stability, reliable delivery systems, and off-target effects. Additional research on the specific molecular mechanisms and more clinical data are still required. This review investigated the biogenesis, regulatory mechanisms, and functions of miRNAs in H. pylori-induced GC, offering novel insights into the potential clinical applications of miRNA-based therapeutics and biomarkers.
胃癌(GC)是全球癌症相关死亡的主要原因,它与遗传、环境和微生物危险因素的结合有关。幽门螺杆菌(H. pylori)被归类为 I 类致癌物,然而,H. pylori 诱导 GC 的确切调节机制尚未完全确定。微小 RNA(miRNA)是一种小的非编码 RNA,通过与靶基因结合来负调控基因表达。miRNA 的失调在人类癌症中至关重要。已经鉴定出大量由 H. pylori 通过复杂的调控网络诱导的异常 miRNA。这些 miRNA 显著影响遗传不稳定性、细胞增殖、凋亡、侵袭、转移、自噬、化疗耐药性和肿瘤微环境,导致 GC 的发生和发展。重要的是,一些与 H. pylori 相关的 miRNA 作为治疗工具和 GC 预防、诊断和预后的生物标志物具有很大的应用前景。然而,miRNA 的临床应用仍处于起步阶段,存在多个问题,包括敏感性和特异性、稳定性、可靠的传递系统和脱靶效应。仍需要更多的研究来探讨具体的分子机制和更多的临床数据。本综述探讨了 miRNA 在 H. pylori 诱导 GC 中的生物发生、调控机制和功能,为 miRNA 治疗和生物标志物的潜在临床应用提供了新的见解。