Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Sadat City, 32897, Egypt.
Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, 11829, Cairo, Egypt.
Med Oncol. 2024 Aug 5;41(9):218. doi: 10.1007/s12032-024-02455-w.
Gastric cancers (GCs) are among the most common and fatal malignancies in the world. Despite our increasing understanding of the molecular mechanisms underlying GC, further biomarkers are still needed for more in-depth examination, focused prognosis, and treatment. GC is one among the long non-coding RNAs, or lncRNAs, that have emerged as key regulators of the pathophysiology of cancer. This comprehensive review focuses on the diverse functions of long noncoding RNAs (lncRNAs) in the development of GC and their interactions with important intracellular signaling pathways. LncRNAs affect GC-related carcinogenic signaling cascades including pathways for EGFR, PI3K/AKT/mTOR, p53, Wnt/β-catenin, JAK/STAT, Hedgehog, NF-κB, and hypoxia-inducible factor. Dysregulated long non-coding RNA (lncRNA) expression has been associated with multiple characteristics of cancer, such as extended growth, apoptosis resistance, enhanced invasion and metastasis, angiogenesis, and therapy resistance. For instance, lncRNAs such as HOTAIR, MALAT1, and H19 promote the development of GC via altering these pathways. Beyond their main roles, GC lncRNAs exhibit potential as diagnostic and prognostic biomarkers. The overview discusses CRISPR/Cas9 genome-modifying methods, antisense oligonucleotides, small molecules, and RNA interference as potential therapeutic approaches to regulate the expression of long noncoding RNAs (lncRNAs). An in-depth discussion of the intricate functions that lncRNAs play in the development of the majority of stomach malignancies is provided in this review. It provides the groundwork for future translational research in lncRNA-based whole processes toward GC by highlighting their carcinogenic effects, regulatory roles in significant signaling cascades, and practical scientific uses as biomarkers and therapeutic targets.
胃癌(GCs)是世界上最常见和最致命的恶性肿瘤之一。尽管我们对 GC 发病机制的分子机制有了越来越多的了解,但仍需要进一步的生物标志物来进行更深入的检查、有针对性的预后和治疗。GC 是长链非编码 RNA(lncRNA)之一,已成为癌症病理生理学的关键调节因子。本综述重点介绍了长链非编码 RNA(lncRNA)在 GC 发展中的多种功能及其与重要细胞内信号通路的相互作用。lncRNAs 影响与 GC 相关的致癌信号级联反应,包括 EGFR、PI3K/AKT/mTOR、p53、Wnt/β-catenin、JAK/STAT、Hedgehog、NF-κB 和缺氧诱导因子。失调的长非编码 RNA(lncRNA)表达与癌症的多种特征相关,如延长生长、抗凋亡、增强侵袭和转移、血管生成和治疗耐药性。例如,HOTAIR、MALAT1 和 H19 等 lncRNAs 通过改变这些途径促进 GC 的发展。除了主要作用外,GC lncRNAs 还具有作为诊断和预后生物标志物的潜力。该综述讨论了 CRISPR/Cas9 基因组修饰方法、反义寡核苷酸、小分子和 RNA 干扰作为调节长非编码 RNA(lncRNA)表达的潜在治疗方法。本文深入讨论了 lncRNA 在大多数胃恶性肿瘤发生发展中所起的复杂作用,通过强调其致癌作用、在重要信号级联中的调节作用以及作为生物标志物和治疗靶点的实际科学用途,为基于 lncRNA 的 GC 全过程的未来转化研究奠定了基础。