Exosomatic miR-1246 Promotes Hepatocellular Carcinoma Progression via FSTL5 and ERK/p38 MAPK Pathway

IF 3.2 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-03-11 DOI:10.1002/jbt.70148

Wen-ju Chen, Ying-jie Dai, Wan-hong Gu, Chun-ling Zhang, Yi-chao Wang

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引用次数: 0

Abstract

Background

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Unfortunately, the effective targeted therapies for HCC are lacking at present. While the regulation of microRNA-1246 (miR-1246) has been identified in HCC, its specific mechanism in exosomes derived from HCC remains elusive. This study aimed to explore the regulation of tumor-derived exosome miR-1246 in HCC cell invasion, migration, proliferation, and epithelial-mesenchymal transition (EMT).

Methods

Exosomes secreted by HepG2 cells were characterized via Western blotting, nanoparticle tracking analysis, and transmission electron microscopy, followed by transfection with a miR-1246 inhibitor. RT-qPCR was employed for measuring the miR-1246 levels. Also, the impacts of the exosome miR-1246 inhibitor on HepG2 cell migration, invasion, proliferation, and EMT were evaluated.

Results

The findings revealed elevated miR-1246 levels in HCC tissues relative to adjacent non-cancerous tissues, with a greater enrichment of miR-1246 in HepG2-derived exosomes than in HepG2 cells. HCC cell invasion, migration, proliferation, and EMT were significantly enhanced by HCC-derived exosomes, while exosomes loaded with miR-1246 inhibitor inhibited these biological functions. Further mechanistic studies illustrated an association of the regulatory role of miR-1246 with FSTL5 and ERK/p38 MAPK signaling.

Conclusion

In conclusion, tumor-derived miR-1246 enters hepatocellular carcinoma cells in the form of exosomes and promotes cancer cell invasion, EMT, and migration. The potential mechanism of miR-1246 is potentially relevant to the targeted gene FSTL5 as well as the ERK/p38 signaling.

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外泌体 miR-1246 通过 FSTL5 和 ERK/p38 MAPK 通路促进肝细胞癌进展

肝细胞癌（HCC）是世界范围内最常见的恶性肿瘤之一。不幸的是，目前HCC缺乏有效的靶向治疗方法。虽然microRNA-1246 （miR-1246）的调控已经在HCC中被确定，但其在HCC衍生的外泌体中的具体机制仍不清楚。本研究旨在探讨肿瘤源性外泌体miR-1246在HCC细胞侵袭、迁移、增殖和上皮-间质转化（EMT）中的调控作用。方法通过Western blotting、纳米颗粒跟踪分析和透射电镜对HepG2细胞分泌的外泌体进行表征，然后转染miR-1246抑制剂。RT-qPCR检测miR-1246水平。此外，我们还评估了外泌体miR-1246抑制剂对HepG2细胞迁移、侵袭、增殖和EMT的影响。研究结果显示，相对于邻近的非癌组织，HCC组织中miR-1246水平升高，HepG2衍生的外泌体中miR-1246的富集程度高于HepG2细胞。HCC来源的外泌体显著增强了HCC细胞的侵袭、迁移、增殖和EMT，而负载miR-1246抑制剂的外泌体则抑制了这些生物学功能。进一步的机制研究表明，miR-1246的调节作用与FSTL5和ERK/p38 MAPK信号传导有关。总之，肿瘤来源的miR-1246以外泌体的形式进入肝癌细胞，促进癌细胞的侵袭、EMT和迁移。miR-1246的潜在机制可能与靶基因FSTL5以及ERK/p38信号通路有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Biochemical and Molecular Toxicology 生物-毒理学

CiteScore

5.80

自引率

2.80%

发文量

277

审稿时长

6-12 weeks

期刊介绍： The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.