Liver cancer is the third leading cause of cancer-related mortality worldwide. Hepatocellular carcinoma (HCC), the most common type of primary liver cancer is driven by complex genetic, epigenetic, and environmental factors. MicroRNAs, a class of naturally-occurring small non-coding RNAs play crucial roles in HCC by simultaneously modulating expression of multiple genes in a fine-tuning manner. Significant progress has been made in understanding how miRNAs influence key oncogenic pathways, including cell proliferation, apoptosis, angiogenesis, and epithelial-mesenchymal transition (EMT), as well as their role in modulating the immune microenvironment in HCC. Due to the unexpected stability of miRNAs in the blood and fixed HCC tumors, recent advancements also highlight their potential as non-invasive diagnostic tools. Restoring or inhibiting specific miRNAs have offered promising strategies for targeted HCC treatment by suppressing malignant hepatocyte growth and enhancing antitumor immunity. In this comprehensive review, we consolidate previous research and provide the latest insights into how miRNAs regulate HCC and their therapeutic and diagnostic potential. We delve into dysregulation of miRNA biogenesis in HCC, the roles of miRNAs in proliferation and apoptosis of malignant hepatocytes, angiogenesis and metastasis of HCC, immune microenvironment in HCC and drug resistance. We also discuss the therapeutic and diagnostic potential of miRNAs and delivery approaches of miRNA drugs to overcome the limitations of current HCC treatment options. By thoroughly summarizing the roles of miRNAs in HCC, our goal is to advance the development of effective therapeutic drugs with minimal adverse effects and to establish precise tools for early diagnosis of HCC.

中文翻译：

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HCC 中的 miRNA、发病机制和靶标


肝癌是全球癌症相关死亡的第三大原因。肝细胞癌 （HCC） 是最常见的原发性肝癌类型，由复杂的遗传、表观遗传和环境因素驱动。MicroRNAs 是一类天然存在的小非编码 RNA，通过以微调方式同时调节多个基因的表达，在 HCC 中起着至关重要的作用。在了解 miRNA 如何影响关键致癌途径方面取得了重大进展，包括细胞增殖、凋亡、血管生成和上皮-间质转化 （EMT），以及它们在调节 HCC 免疫微环境中的作用。由于 miRNA 在血液和固定 HCC 肿瘤中的意外稳定性，最近的进展也凸显了它们作为非侵入性诊断工具的潜力。恢复或抑制特异性 miRNA 通过抑制恶性肝细胞生长和增强抗肿瘤免疫，为靶向 HCC 治疗提供了有前途的策略。在这篇全面的综述中，我们整合了以前的研究，并提供了有关 miRNA 如何调节 HCC 及其治疗和诊断潜力的最新见解。我们深入研究了 HCC 中 miRNA 生物发生的失调、miRNAs 在恶性肝细胞增殖和凋亡中的作用、HCC 的血管生成和转移、HCC 中的免疫微环境和耐药性。我们还讨论了 miRNA 的治疗和诊断潜力以及 miRNA 药物的递送方法，以克服当前 HCC 治疗方案的局限性。通过全面总结 miRNA 在 HCC 中的作用，我们的目标是推进不良反应最小的有效治疗药物的开发，并为 HCC 的早期诊断建立精确的工具。