ArticleAnnals of gastroenterological surgery2024
Lenvatinib-resistant hepatocellular carcinoma promotes malignant potential of tumor-associated macrophages via exosomal miR-301a-3p.
Article in Annals of gastroenterological surgery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Molecular mechanisms of tumor-associated macrophages in hepatocellular carcinoma development and therapy.World journal of gastroenterology · 2026Review
- Tumor Endothelial Cells Induce M2 Macrophage Polarization via IL-4, Enhancing Tumor Growth in Hepatocellular Carcinoma.Cancer science · 2025Article
- Exosome-derived hsa_circ_0007132 promotes lenvatinib resistance by inhibiting the ubiquitin-mediated degradation of NONO.Non-coding RNA research · 2025Article
- Crosstalk between exosomes and tumor-associated macrophages in hepatocellular carcinoma: implication for cancer progression and therapy.Frontiers in immunology · 2025Review
- Lenvatinib-resistant hepatocellular carcinoma promotes malignant potential of tumor-associated macrophages via exosomal miR-301a-3p.Annals of gastroenterological surgery · 2024Article
- [Hepatocellular carcinoma cells induce M2 macrophage polarization through upregulation of ANXA2 and ANXA5 expression].Nan fang yi ke da xue xue bao = Journal of Southern Medical UniversityArticle
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Authors and funding
8 authors.
Funding
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Abstract
Background: The interactions between cancer cells and tumor-associated macrophages (TAMs) via microRNAs (miRNAs) play crucial roles in malignant potential and drug resistance. However, it remains unclear how lenvatinib-resistant hepatocellular carcinoma (LR HCC) promotes TAM tumor biology. Here we investigated the crosstalk between LR HCC cells and TAMs for cancer progression and lenvatinib resistance, focusing on an exosomal miRNA. Methods: We used two bioinformatics software programs to identify miRNAs that target PTEN in gastrointestinal cancers, then investigated exosomal miRNA expression in LR HCC conditioned medium (CM). After modifying TAMs with LR HCC CM (LR TAM), macrophage phenotype and PTEN-Nrf2 signaling pathway component expression were analyzed in LR TAMs. The malignant potential and drug resistance were investigated in naïve HCC cells cultured with LR TAM CM. Results: LR HCC cells highly induced M2-like properties in macrophages compared with naïve HCC cells. Exosomal miR-301a-3p expression was increased in LR HCC CM, with higher activation of the PTEN/PI3K/GSK3β/Nrf2 signaling pathway in LR TAMs. Naïve HCC cells were educated with LR TAM CM to promote malignant potential and lenvatinib resistance. Inhibition of exosomal miR-301a-3p prevented the malignant potential of LR TAMs. Activation of Nrf2 signaling by LR HCC cell-derived exosomal miR-301a-3p skewed the transformation of macrophages to the M2 phenotype. Conclusion: Our study provides new findings on the role of miR-301a-3p, suggesting it is a promising therapeutic target to improve HCC lenvatinib resistance.
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