Hepatocellular carcinoma (HCC) is a predominant malignancy with increasing incidences and mortalities worldwide. In Western countries, the progressive affirmation of Non-alcoholic Fatty Liver Disease (NAFLD) as the main chronic liver disorder in which HCC occurrence is appreciable even in non-cirrhotic stages, constitutes a real health emergency. In light of this, a further comprehension of molecular pathways supporting HCC onset and progression represents a current research challenge to achieve more tailored prognostic models and appropriate therapeutic approaches. RNA non-coding transcripts (ncRNAs) are involved in the regulation of several cancer-related processes, including HCC. When dysregulated, these molecules, conventionally classified as “small ncRNAs” (sncRNAs) and “long ncRNAs” (lncRNAs) have been reported to markedly influence HCC-related progression mechanisms. In this review, we describe the main dysregulated ncRNAs and the relative molecular pathways involved in HCC progression, analyzing their implications in certain etiologically related contexts, and their applicability in clinical practice as novel diagnostic, prognostic, and therapeutic tools. Finally, given the growing evidence supporting the immune system response, the oxidative stress-regulated mechanisms, and the gut microbiota composition as relevant emerging elements mutually influencing liver-cancerogenesis processes, we investigate the relationship of ncRNAs with this triad, shedding light on novel pathogenetic frontiers of HCC progression.
肝细胞癌（HCC）是一种主要的恶性肿瘤，其全球发病率和死亡率持续上升。在西方国家，非酒精性脂肪性肝病（NAFLD）已逐渐被确认为主要的慢性肝病，其甚至在非肝硬化阶段即可发生HCC，这构成了现实的公共卫生紧急状况。鉴于此，进一步理解支持HCC发生与进展的分子通路，成为当前研究的重要挑战，旨在建立更精准的预后模型和制定更合适的治疗策略。非编码RNA（ncRNA）参与包括HCC在内的多种癌症相关过程的调控。当这些通常被归类为“小非编码RNA”（sncRNA）和“长非编码RNA”（lncRNA）的分子发生失调时，已被证实能显著影响HCC相关的进展机制。本综述描述了HCC进展中主要失调的ncRNA及其相关分子通路，分析了它们在特定病因相关背景下的作用，以及作为新型诊断、预后和治疗工具在临床实践中的适用性。最后，鉴于越来越多的证据表明免疫系统反应、氧化应激调控机制及肠道菌群组成是相互影响肝癌发生过程的重要新兴因素，我们探讨了ncRNA与这三者之间的关系，从而揭示了HCC进展的新发病机制前沿。
肿瘤(癌症)患者之家