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微小RNA通过多种信号通路交叉调控肝细胞癌上皮-间质转化过程的潜在机制及靶向治疗策略

The underlying mechanism and targeted therapy strategy of miRNAs cross-regulating EMT process through multiple signaling pathways in hepatocellular carcinoma.

作者信息

Chen Juan, He Fuguo, Peng Hong, Guo Jinjun

机构信息

Department of Pathology, Bishan Hospital of Chongqing Medical University, Chongqing, China.

Department of Gastroenterology, Bishan Hospital of Chongqing Medical University, Chongqing, China.

出版信息

Front Mol Biosci. 2024 Mar 22;11:1378386. doi: 10.3389/fmolb.2024.1378386. eCollection 2024.

Abstract

The consistent notion holds that hepatocellular carcinoma (HCC) initiation, progression, and clinical treatment failure treatment failure are affected by the accumulation of various genetic and epigenetic alterations. MicroRNAs (miRNAs) play an irreplaceable role in a variety of physiological and pathological states. meanwhile, epithelial-mesenchymal transition (EMT) is a crucial biological process that controls the development of HCC. miRNAs regulate the intermediation state of EMTor mesenchymal-epithelial transition (MTE)thereby regulating HCC progression. Notably, miRNAs regulate key HCC-related molecular pathways, including the Wnt/β-catenin pathway, PTEN/PI3K/AKT pathway, TGF-β pathway, and RAS/MAPK pathway. Therefore, we comprehensively reviewed how miRNAs produce EMT effects by multiple signaling pathways and their potential significance in the pathogenesis and treatment response of HCC. emphasizing their molecular pathways and progression in HCC initiation. Additionally, we also pay attention to regulatory mechanisms that are partially independent of signaling pathways. Finally, we summarize and propose miRNA-targeted therapy and diagnosis and defense strategies forHCC. The identification of the mechanism leading to the activation of EMT programs during HCC disease processes also provides a new protocol for the plasticity of distinct cellular phenotypes and possible therapeutic interventions. Consequently, we summarize the latest progress in this direction, with a promising path for further insight into this fast-moving field.

摘要

一致的观点认为,肝细胞癌(HCC)的起始、进展以及临床治疗失败均受多种基因和表观遗传改变积累的影响。微小RNA(miRNA)在多种生理和病理状态中发挥着不可替代的作用。同时,上皮-间质转化(EMT)是控制HCC发展的关键生物学过程。miRNA调节EMT或间质-上皮转化(MET)的中间状态,从而调节HCC进展。值得注意的是,miRNA调节关键的HCC相关分子途径,包括Wnt/β-连环蛋白途径、PTEN/PI3K/AKT途径、TGF-β途径和RAS/MAPK途径。因此,我们全面综述了miRNA如何通过多种信号通路产生EMT效应及其在HCC发病机制和治疗反应中的潜在意义,强调它们在HCC起始中的分子途径和进展。此外,我们还关注部分独立于信号通路的调控机制。最后,我们总结并提出针对HCC的miRNA靶向治疗、诊断和防御策略。确定HCC疾病过程中导致EMT程序激活的机制,也为不同细胞表型的可塑性和可能的治疗干预提供了新方案。因此,我们总结了这一方向的最新进展,为进一步深入了解这个快速发展的领域提供了一条有前景的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb40/10995332/a24ac46a1105/fmolb-11-1378386-g001.jpg

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