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肝细胞癌进展的表观遗传调控:miRNAs 作为治疗、诊断和预后因素。

Epigenetic regulation of hepatocellular carcinoma progression: MicroRNAs as therapeutic, diagnostic and prognostic factors.

机构信息

Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

出版信息

Int J Biochem Cell Biol. 2024 May;170:106566. doi: 10.1016/j.biocel.2024.106566. Epub 2024 Mar 20.

Abstract

Hepatocellular carcinoma (HCC), a significant challenge for public healthcare systems in developed Western countries including the USA, Canada, and the UK, is influenced by different risk factors including hepatitis virus infections, alcoholism, and smoking. The disruption in the balance of microRNAs (miRNAs) plays a vital function in tumorigenesis, given their function as regulators in numerous signaling networks. These miRNAs, which are mature and active in the cytoplasm, work by reducing the expression of target genes through their impact on mRNAs. MiRNAs are particularly significant in HCC as they regulate key aspects of the tumor, like proliferation and invasion. Additionally, during treatment phases such as chemotherapy and radiotherapy, the levels of miRNAs are key determinants. Pre-clinical experiments have demonstrated that altered miRNA expression contributes to HCC development, metastasis, drug resistance, and radio-resistance, highlighting related molecular pathways and processes like MMPs, EMT, apoptosis, and autophagy. Furthermore, the regulatory role of miRNAs in HCC extends beyond their immediate function, as they are also influenced by other epigenetic factors like lncRNAs and circular RNAs (circRNAs), as discussed in recent reviews. Applying these discoveries in predicting the prognosis of HCC could mark a significant advancement in the therapy of this disease.

摘要

肝细胞癌 (HCC) 是美国、加拿大和英国等发达国家公共医疗体系面临的重大挑战,其发病受到多种因素的影响,包括肝炎病毒感染、酗酒和吸烟等。微 RNA (miRNA) 的平衡失调在肿瘤发生中起着至关重要的作用,因为它们作为众多信号网络的调节剂发挥作用。这些成熟并在细胞质中活跃的 miRNA 通过影响 mRNAs 来减少靶基因的表达。miRNA 在 HCC 中尤为重要,因为它们调节肿瘤的关键方面,如增殖和侵袭。此外,在化疗和放疗等治疗阶段,miRNA 的水平是关键决定因素。临床前实验表明,miRNA 表达的改变导致 HCC 的发展、转移、耐药性和放射抗性,突出了相关的分子途径和过程,如 MMPs、EMT、细胞凋亡和自噬。此外,miRNA 在 HCC 中的调控作用不仅限于其直接功能,正如最近的综述中所讨论的,它们还受到其他表观遗传因子如 lncRNA 和环状 RNA (circRNA) 的影响。将这些发现应用于预测 HCC 的预后可能标志着该疾病治疗的重大进展。

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