Ghionescu Alina-Veronica, Sorop Andrei, Dima Simona Olimpia
Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania.
Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest, Romania.
Front Pharmacol. 2023 Sep 11;14:1270425. doi: 10.3389/fphar.2023.1270425. eCollection 2023.
Hepatocellular carcinoma (HCC) remains a major health problem worldwide, being the leading cause of cancer-related deaths, with limited treatment options, especially in its advanced stages. Tumor resistance is closely associated with the activation of the EMT phenomenon and its reversal, being modulated by different molecules, including noncoding RNAs (ncRNAs). Noncoding RNAs have the potential to function as both tumor suppressors and oncogenic molecules, controlling the malignant potential of HCC cells. Basically, these molecules circulate in the tumor microenvironment, encapsulated in exosomes. Their impact on cell biology is more significant than originally expected, which makes related research rather complex. The temporal and spatial expression patterns, precise roles and mechanisms of specific ncRNAs encapsulated in exosomes remain primarily unknown in different stages of the disease. This review aims to highlight the recent advances in ncRNAs related to EMT and classifies the described mechanism as direct and indirect, for a better summarization. Moreover, we provide an overview of current research on the role of ncRNAs in several drug resistance-related pathways, including the emergence of resistance to sorafenib, doxorubicin, cisplatin and paclitaxel therapy. Nevertheless, we comprehensively discuss the underlying regulatory mechanisms of exosomal ncRNAs in EMT-HCC via intercellular communication pathways.
肝细胞癌（HCC）仍然是全球主要的健康问题，是癌症相关死亡的主要原因，治疗选择有限，尤其是在晚期。肿瘤耐药性与上皮-间质转化（EMT）现象的激活及其逆转密切相关，受包括非编码RNA（ncRNAs）在内的不同分子调控。非编码RNA既有作为肿瘤抑制因子的功能，也有致癌分子的功能，控制着肝癌细胞的恶性潜能。基本上，这些分子在肿瘤微环境中循环，包裹在外泌体中。它们对细胞生物学的影响比最初预期的更为显著，这使得相关研究相当复杂。在疾病的不同阶段，外泌体中包裹的特定ncRNAs的时空表达模式、精确作用和机制仍然基本未知。本综述旨在突出与EMT相关的ncRNAs的最新进展，并将所描述的机制分为直接和间接机制，以便更好地总结。此外，我们概述了目前关于ncRNAs在几种与耐药相关途径中的作用的研究，包括对索拉非尼、阿霉素、顺铂和紫杉醇治疗产生耐药性的情况。然而，我们通过细胞间通讯途径全面讨论了外泌体ncRNAs在EMT-HCC中的潜在调控机制。
