ArticleInternational journal of molecular sciences2023
Hepatocellular Carcinoma Cell-Derived Exosomal miR-21-5p Induces Macrophage M2 Polarization by Targeting RhoB.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 58 citations in OpenAlex.
- Unifying and unique roles of non-coding RNA biomarkers in liver and heart fibrosis.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Review
- Emerging role of microRNAs as modulators of the tumor immune microenvironment.Journal for immunotherapy of cancer · 2026Review
- DNA Hypomethylation ofInternational journal of molecular sciences · 2026Article
- Review
- Melanoma exosomal miR-708-5p promotes macrophage M2 polarization and cancer metastasis.Cell death & disease · 2026Article
- Roles of exosome-mediated macrophage polarization in the hepatocellular carcinoma progression.Frontiers in immunology · 2026Review
- CCT2 Orchestrates Glycolysis and Exosome-Mediated M2 Macrophage Polarization in HCC tumorigenesis.International journal of biological sciences · 2026Article
- Rewiring tumor-associated macrophages in hepatocellular carcinoma.Frontiers in immunology · 2026Review
- Research progress on the mechanism, diagnosis, and treatment of exosomal miRNA in chronic prostatitis.Frontiers in immunology · 2026Review
- From immune desert to hot tumor: the tripartite synergy of tumor microenvironment-exosomes-immunogenic cell death in pioneering solutions.Frontiers in immunology · 2026Review
- Exosome-Mediated Regulation of Aerobic Glycolysis in Hepatocellular Carcinoma: Mechanisms and Therapeutic Implications.Journal of hepatocellular carcinoma · 2026Review
- Molecular Docking and Single-Cell RNA-Seq Analysis IdentifyCurrent medicinal chemistry · 2026Article
- Integrative Analysis of miR-21, PTEN, and Immune Signatures in Colorectal Cancer.International journal of molecular sciences · 2025Article
- Exosomal regulation of cellular reprogramming and polarization in the tumor microenvironment.Cancer cell international · 2025Review
- Advances in Tumor-Derived Exosomal Non-Coding RNAs Regulating M2 Macrophage Polarization: Molecular Mechanisms and Signaling Pathway.Cancer medicine · 2025Review
- Exosomal miRNAs: Key Regulators of the Tumor Microenvironment and Cancer Stem Cells.International journal of molecular sciences · 2025Review
- MicroRNA Landscape in Hepatocellular Carcinoma: Metabolic Re-Wiring, Predictive and Diagnostic Biomarkers, and Emerging Therapeutic Targets.Biomedicines · 2025Review
- The recent progress of tumor cell-derived exosomes in the pathogenesis, diagnosis and therapeutic strategies of tumors.Journal of translational medicine · 2025Review
- Targeting tumor-associated macrophages to overcome immune checkpoint inhibitor resistance in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2025Review
- Molecular interaction of human papilloma virus (HPV) with microRANs: insights into the development of cervical cancer and treatment approaches.Infectious agents and cancer · 2025Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
M2-like polarized tumor-associated macrophages (TAMs) are the major component of infiltrating immune cells in hepatocellular carcinoma (HCC), which have been proved to exhibit significant immunosuppressive and pro-tumoral effects. However, the underlying mechanism of the tumor microenvironment (TME) educating TAMs to express M2-like phenotypes is still not fully understood. Here, we report that HCC-derived exosomes are involved in intercellular communications and exhibit a greater capacity to mediate TAMs' phenotypic differentiation. In our study, HCC cell-derived exosomes were collected and used to treat THP-1 cells in vitro. Quantitative polymerase chain reaction (qPCR) results showed that the exosomes significantly promoted THP-1 macrophages to differentiate into M2-like macrophages, which have a high production of transforming growth factor-β (TGF-β) and interleukin (IL)-10. The analysis of bioinformatics indicated that exosomal miR-21-5p is closely related to TAM differentiation and is associated with unfavorable prognosis in HCC. Overexpressing miR-21-5p in human monocyte-derived leukemia (THP-1) cells induced down-regulation of IL-1β levels; however, it enhanced production of IL-10 and promoted the malignant growth of HCC cells in vitro. A reporter assay confirmed that miR-21-5p directly targeted Ras homolog family member B (RhoB) 3'-untranslatedregion (UTR) in THP-1 cells. Downregulated RhoB levels in THP-1 cells would weaken mitogen-activated protein kinase (MAPK) axis signaling pathways. Taken together, tumor-derived miR-21-5p promote the malignant advance of HCC, which mediated intercellular crosstalk between tumor cells and macrophages. Targeting M2-like TAMs and intercepting their associated signaling pathways would provide potentially specific and novel therapeutic approaches for HCC treatment.
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