ArticleMolecular cancer2021
Epigenetic silencing of miR-144/451a cluster contributes to HCC progression via paracrine HGF/MIF-mediated TAM remodeling.
Article in Molecular cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 129 citations in OpenAlex.
- DNA Methylation as a Programmable Information Layer: From Molecular Marks to Disease State Engineering.International journal of molecular sciences · 2026Review
- β-glucan elicits APOE-dependent peripheral trained immunity to suppress hepatocellular carcinoma.Journal for immunotherapy of cancer · 2026Article
- miR-144 targets in myocardial hypertrophy and coronary microvascular dysfunction in hypertrophic cardiomyopathy: molecular research meets imaging.Basic research in cardiology · 2026Article
- FBXO22 promotes hepatocellular carcinoma progression via paracrine myo‑inositol‑induced M2‑type polarization of macrophages.International journal of molecular medicine · 2026Article
- Roles of exosome-mediated macrophage polarization in the hepatocellular carcinoma progression.Frontiers in immunology · 2026Review
- Hypoxic Endothelial-Cell-Derived Exosomal lnc-DKK3 Reprograms Tumor-Associated Macrophages via USP47/PD-L1/RelA Axis to Promote Glioma Progression.Research (Washington, D.C.) · 2026Article
- Identification and validation of prognostic markers for cuproptosis-related macrophage polarization genes in hepatocellular carcinoma.Discover oncology · 2025Article
- Integrated single-cell RNA-seq analysis reveals that EZH2 regulates the MIF-CD74 axis to modulate T cell activation and exhaustion in hepatocellular carcinoma.Journal of translational medicine · 2025Article
- MicroRNA Landscape in Hepatocellular Carcinoma: Metabolic Re-Wiring, Predictive and Diagnostic Biomarkers, and Emerging Therapeutic Targets.Biomedicines · 2025Review
- Targeting tumor-associated macrophages to overcome immune checkpoint inhibitor resistance in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2025Review
- Macrophage Signaling Pathways in Health and Disease: From Bench to Bedside Applications.MedComm · 2025Review
- The epigenetic basis of hepatocellular carcinoma - mechanisms and potential directions for biomarkers and therapeutics.British journal of cancer · 2025Review
- MiR-451a attenuates hepatic steatosis and hepatitis C virus replication by targeting glycerol kinase.Journal of translational medicine · 2025Article
- Macrophage migration inhibitory factor (MIF) and the tumor ecosystem: a tale of inflammation, immune escape, and tumor growth.Frontiers in immunology · 2025Review
- Methionine restriction promotes the polarization of macrophages towards M1 and the immunotherapy effect of PD-L1/PD-1 blockades by inhibiting the secretion of MIF by gastric carcinoma cells.Translational oncology · 2025Article
- Ambivalent roles of miRNAs in cancer development via modulating tumor-associated innate immune cells.BioImpacts : BI · 2025Review
- Epigenetic Impact of Curcumin and Thymoquinone on Cancer Therapeutics.Current medicinal chemistry · 2025Review
- miRNAs in HCC, pathogenesis, and targets.Hepatology (Baltimore, Md.) · 2024Article
- Epigenetic modifications involving ncRNAs in digestive system cancers: focus on histone modification.Clinical epigenetics · 2024Review
- MicroRNAs in Hepatocellular Carcinoma Pathogenesis: Insights into Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2024Review
14 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsHepatocellular carcinoma (HCC) is among the malignancies with the highest mortality. The key regulators and their interactive network in HCC pathogenesis remain unclear. Along with genetic mutations, aberrant epigenetic paradigms, including deregulated microRNAs (miRNAs), exert profound impacts on hepatocyte transformation and tumor microenvironment remodeling; however, the underlying mechanisms are largely uncharacterized.
methodsWe performed RNA sequencing on HCC specimens and bioinformatic analyses to identify tumor-associated miRNAs. The miRNA functional targets and their effects on tumor-infiltrating immune cells were investigated. The upstream events, particularly the epigenetic mechanisms responsible for miRNA deregulation in HCC, were explored.
resultsThe miR-144/miR-451a cluster was downregulated in HCC and predicted a better HCC patient prognosis. These miRNAs promoted macrophage M1 polarization and antitumor activity by targeting hepatocyte growth factor (HGF) and macrophage migration inhibitory factor (MIF). The miR-144/miR-451a cluster and EZH2, the catalytic subunit of polycomb repressive complex (PRC2), formed a feedback circuit in which miR-144 targeted EZH2 and PRC2 epigenetically repressed the miRNA genes via histone H3K27 methylation of the promoter. The miRNA cluster was coordinately silenced by distal enhancer hypermethylation, disrupting chromatin loop formation and enhancer-promoter interactions. Clinical examinations indicated that methylation of this chromatin region is a potential HCC biomarker.
conclusionsOur study revealed novel mechanisms underlying miR-144/miR-451a cluster deregulation and the crosstalk between malignant cells and tumor-associated macrophages (TAMs) in HCC, providing new insights into HCC pathogenesis and diagnostic strategies.
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