Hamdy Nadia M, Sallam Al-Aliaa M, Elazazy Ola, Kabel Ahmed M, Salama Rania M, Gouhar Shaimaa A, El-Daly Sherien M, Darwish Samar F
Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Abassia, Cairo, 11566, Egypt.
Biochemistry Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, 11829, Cairo, Egypt.
Naunyn Schmiedebergs Arch Pharmacol. 2025 May 23. doi: 10.1007/s00210-025-04285-7.
The most prevalent form of primary liver cancer and one of the chief drivers of cancer-related mortality globally is hepatocellular carcinoma (HCC). Imminent evidence has indicated that non-coding RNAs (ncRNAs) play an integral part in the development and propagation of HCC. RNA stabilization, transcription regulation, chromatin and genomic architecture remodeling, enhancer-associated activity, and other varied properties set long intergenic ncRNA (lincRNA) genes apart from messenger RNA (mRNA)-encoding genes. Through a variety of processes, lincRNAs may generally be used to fine-tune the transcription of nearby genes with exceptional tissue specificity, underscoring our quickly developing knowledge of the non-coding genome. Through their binding with divergent cell targets, some HCC-related ncRNAs have been demonstrated to exhibit abnormal expression, contribute to malignant growth, evade apoptosis, and have invasive potential. Therefore, a better comprehension of lincRNA dysregulation might offer novel perspectives on the pathophysiology of HCC as well as innovative instruments for the early detection and management of HCC. In the present review, we provide an overview of the increasing relevance of lincRNAs as a major contributor to the pathophysiology of HCC, emphasizing their influence on signaling pathways implicated in the development, progression, and response to treatment of tumors. In addition, we go over the new approaches that target lincRNAs for HCC treatment as well as the possible therapeutic uses of lincRNAs as prognostic and diagnostic biomarkers for HCC.
肝细胞癌（HCC）是原发性肝癌最常见的形式，也是全球癌症相关死亡的主要驱动因素之一。已有确凿证据表明，非编码RNA（ncRNA）在HCC的发生和发展中起着不可或缺的作用。RNA稳定性、转录调控、染色质和基因组结构重塑、增强子相关活性以及其他各种特性，使长链基因间非编码RNA（lincRNA）基因有别于信使RNA（mRNA）编码基因。通过多种过程，lincRNAs通常可用于以特殊的组织特异性微调附近基因的转录，这突出了我们对非编码基因组的快速深入了解。通过与不同细胞靶点结合，一些与HCC相关的ncRNAs已被证明表现出异常表达，促进恶性生长，逃避凋亡，并具有侵袭潜力。因此，更好地理解lincRNA失调可能为HCC的病理生理学提供新的视角，以及为HCC的早期检测和管理提供创新工具。在本综述中，我们概述了lincRNAs作为HCC病理生理学主要贡献者的重要性日益增加，强调它们对参与肿瘤发生、发展和治疗反应的信号通路的影响。此外，我们还探讨了针对lincRNAs进行HCC治疗的新方法，以及lincRNAs作为HCC预后和诊断生物标志物的可能治疗用途。
