ArticleJournal of experimental & clinical cancer research : CR2022
Tumor associated macrophages-derived exosomes facilitate hepatocellular carcinoma malignance by transferring lncMMPA to tumor cells and activating glycolysis pathway.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 1 of them a synthesis that pooled it.
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Who cites it
95 citing papers in PubMed, 1 synthesis or guideline pooled it, 130 citations in OpenAlex.
- Unveiling the functional paradigm of exosome-derived long non-coding RNAs (lncRNAs) in cancer: based on a narrative review and systematic review.Journal of cancer research and clinical oncology · 2023Pooled it
- Functional heterogeneity of exosomes in hepatocellular carcinoma (Review).Experimental and therapeutic medicine · 2026Review
- miRNA-lncRNA Cross-Regulation Landscape in Cancer: From Molecular Mechanisms to Therapeutic and Diagnostic Applications.Cancers · 2026Review
- The regulatory role of circGDI2 in hepatocellular carcinoma proliferation and glycolysis with the involvement of m6A modification.Non-coding RNA research · 2026Article
- Extracellular vesicles as modulators of cancer metabolism and microenvironment.Extracellular vesicles and circulating nucleic acids · 2026Review
- OTUB2/ALYREF axis modulates the docetaxel resistance of castration-resistant prostate cancer via upregulating ABCG4-mediated drug efflux.International journal of biological sciences · 2026Article
- Polarization-Specific Macrophage-Derived Extracellular Vesicles: Molecular Cargo, Tumor Microenvironment Remodeling, and Therapeutic Opportunities.International journal of nanomedicine · 2026Review
- Roles of exosome-mediated macrophage polarization in the hepatocellular carcinoma progression.Frontiers in immunology · 2026Review
- Tumor-associated macrophages in hepatocellular carcinoma: Cellular plasticity and therapy resistance in crosstalk.Journal of pharmaceutical analysis · 2026Review
- Exosome-Mediated Regulation of Aerobic Glycolysis in Hepatocellular Carcinoma: Mechanisms and Therapeutic Implications.Journal of hepatocellular carcinoma · 2026Review
- Macrophage-derived long non-coding RNAs in cancer: pioneering targets for immune modulation and personalized therapy.Frontiers in immunology · 2026Review
- Metabolic symbiosis and competition: the dual nature of TAM-tumor cell cross-talk in tumor progression.Frontiers in oncology · 2026Review
- Review
- Exosomal regulation of cellular reprogramming and polarization in the tumor microenvironment.Cancer cell international · 2025Review
- Long non-coding RNAs in cancer glycolysis and metabolism: mechanisms and translational opportunities.Cell death & disease · 2025Review
- Exosomal miR-3126-5p derived from cancer-associated fibroblasts facilitates glycolysis to accelerate NSCLC progression by targeting KLF13 to activate the SH2B1/IRS1 axis.Clinical and translational medicine · 2025Article
- Identification Of Protein Cargo in Extracellular Vesicles from Macrophages in Progressing and Regressing Tumors.bioRxiv : the preprint server for biology · 2025Article
- Exosomes in cancer metabolism and drug resistance: A review.Biomolecules & biomedicine · 2025Review
- CCDC137/DGCR8 axis promotes aerobic glycolysis in hepatocellular carcinoma via activation of the AKT/mTOR signaling pathway.European journal of medical research · 2025Article
- Role of lncRNA NONMMUT104330.1-miR-709-DDX58 axis in mediating immunomodulatory effects of enoxaparin sodium bone cement on macrophage polarization and inflammatory response.Journal of orthopaedic surgery and research · 2025Article
35 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundTumor-associated macrophages (TAMs), which form a large part of the tumor microenvironment, are normally regulated by metabolic reprogramming. However, the potential mechanisms of the immune-metabolism interaction between hepatocellular carcinoma (HCC) cells and TAMs remain unclear.
methodsThe candidate long non-coding RNAs (lncRNAs) were screened by Smart-seq based scRNA-seq method and then validated by qPCR. Immunostaining analysis was done to examine the levels of markers for TAMs and glycolysis. Exosomes from primary TAMs of human HCC tissues were isolated by centrifugation, and their internalization with lncRNAs was confirmed by immunofluorescence. The underlying mechanism of TAMs-derived exosomal lncRNA to HCC was confirmed by luciferase reporter assay and RNA immunoprecipitation. Metabolism regulation was evaluated through glucose consumption, lactate productions and extracellular acidification rates (ECARs). Mouse xenograft models were used to elucidate the in vivo effect of candidate lncRNAs on tumor growth.
resultsTAMs augment the aerobic glycolysis in HCC cells and their proliferation by the extracellular exosome transmission of a myeloid-derived lncRNA, M2 macrophage polarization associated lncRNA (lncMMPA). Mechanistically, lncMMPA not only could polarize M2 macrophage, but also could act as an microRNA sponge to interact with miR-548 s and increase the mRNA level of ALDH1A3, then further promote glucose metabolism and cell proliferation in HCC. Moreover, lncMMPA increased HCC cell multiplication through interacting with miR-548 s in vivo. Clinically, lncMMPA expression associates with glycolysis in TAMs and reduced survival of HCC patients.
conclusionLncMMPA plays an important role in regulating HCC malignancy and metabolic reprogramming of miR-548 s/ALDH1A3 pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.