Romeo Mario, Dallio Marcello, Scognamiglio Flavia, Ventriglia Lorenzo, Cipullo Marina, Coppola Annachiara, Tammaro Chiara, Scafuro Giuseppe, Iodice Patrizia, Federico Alessandro
Hepatogastroenterology Division, Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Piazza Miraglia 2, 80138 Naples, Italy.
Biochemistry Division, Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Piazza Miraglia 2, 80138 Naples, Italy.
Cancers (Basel). 2023 Oct 27;15(21):5178. doi: 10.3390/cancers15215178.
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，在全球范围内其发病率和死亡率都在不断上升。在西方国家，非酒精性脂肪性肝病（NAFLD）作为主要的慢性肝脏疾病逐渐得到确认，在这种疾病中，即使在非肝硬化阶段，HCC的发生也较为显著，这构成了一个真正的健康紧急情况。鉴于此，进一步了解支持HCC发生和发展的分子途径是当前的一项研究挑战，以实现更具针对性的预后模型和合适的治疗方法。RNA非编码转录本（ncRNAs）参与了包括HCC在内的多种癌症相关过程的调控。当这些分子失调时，传统上被归类为“小ncRNAs”（sncRNAs）和“长ncRNAs”（lncRNAs）的这些分子已被报道会显著影响HCC相关的进展机制。在这篇综述中，我们描述了参与HCC进展的主要失调ncRNAs及其相关分子途径，分析了它们在某些病因相关背景下的意义，以及它们作为新型诊断、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支持免疫系统反应、氧化应激调节机制和肠道微生物群组成是相互影响肝癌发生过程的相关新兴因素，我们研究了ncRNAs与这三者之间的关系，揭示了HCC进展的新发病机制前沿。
