ArticleMolecular medicine (Cambridge, Mass.)2023
LINC00963 promotes the malignancy and metastasis of lung adenocarcinoma by stabilizing Zeb1 and exosomes-induced M2 macrophage polarization.
Article in Molecular medicine (Cambridge, Mass.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 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
- Exploring exosomal lncRNAs: unlocking the molecular code of tumor metastasis and drug resistance.Cancer cell international · 2025Review
- Advances in Tumor-Derived Exosomal Non-Coding RNAs Regulating M2 Macrophage Polarization: Molecular Mechanisms and Signaling Pathway.Cancer medicine · 2025Review
- Exosomes promote pre-metastatic niche formation in lung cancer.Cancer cell international · 2025Review
- The role of long non-coding RNAs in lung cancer metastasis: Molecular mechanisms, pathogenesis and clinical implications.Clinical and translational medicine · 2025Review
- HNRNPA2B1: a novel target in pulmonary arterial hypertension.Frontiers in cardiovascular medicine · 2025Review
- Exosome tropism and various pathways in lung cancer metastasis.Frontiers in immunology · 2025Review
- Super-enhancer-associated LINC00963 promotes metastasis of gastric cancer through epithelial-mesenchymal transition.PloS one · 2025Article
- Circ_CIT Promotes Nasopharyngeal Carcinoma Progression and Macrophage M2 Polarization Through miR-409-3p/ZEB1 Axis.Cancer management and research · 2025Article
- Decoding the Tumor Microenvironment: Exosome-Mediated Macrophage Polarization and Therapeutic Frontiers.International journal of biological sciences · 2025Review
- LINC00963 Promotes Cisplatin Resistance in Esophageal Squamous Cell Carcinoma by Interacting with miR-10a to Upregulate SKA1 Expression.Applied biochemistry and biotechnology · 2024Article
- Non-coding RNAs and exosomal non-coding RNAs in lung cancer: insights into their functions.Frontiers in cell and developmental biology · 2024Review
- Exosomes: efficient macrophage-related immunomodulators in chronic lung diseases.Frontiers in cell and developmental biology · 2024Review
- Engineered exosomes-based theranostic strategy for tumor metastasis and recurrence.Asian journal of pharmaceutical sciences · 2023Review
- Article
- Exosomes: Diagnostic and Therapeutic Implications in Cancer.Pharmaceutics · 2023Review
- Exosomal Non-Coding RNAs: Novel Regulators of Macrophage-Linked Intercellular Communication in Lung Cancer and Inflammatory Lung Diseases.Biomolecules · 2023Review
- Landscape of tumor and immune system cells-derived exosomes in lung cancer: mediators of antitumor immunity regulation.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLong intergenic non-coding RNA 00963 (LINC00963) is an oncogenic lncRNA in human cancers. However, little is known on how it impacts the pathogenesis of lung adenocarcinoma (LUAD).
methodsBiological effects on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) were examined by CCK-8, colony formation, EdU incorporation, transwell, and immunofluorescence assays, respectively. Macrophage polarization was evaluated by flow cytometry. Ubiquitination of Zeb1 was examined by co-immunoprecipitation. The location of LINC00963 in LUAD tissues and cell lines was tested by FISH assay. The LINC00963/HNRNPA2B1/Siah1 mRNA complex interaction was verified using RNA pull-down and immunoprecipitation assays. The exact roles of LINC00963 were further validated in metastasis and xenograft models.
resultsHigher LINC00963 expression in LUAD patients positively correlated with shorter overall survival, higher stages, and metastasis. LINC00963 mainly localized in the cytoplasm and aggravated malignant phenotypes of LUAD cells in vitro and metastasis in vivo. Mechanistically, LINC00963 directly interacted HNRNPA2B1 protein to trigger the degradation of Siah1 mRNA, which inhibited the ubiquitination and degradation of Zeb1. Moreover, exosomal LINC00963 derived from LUAD cells induced M2 macrophage polarization and promoted LUAD growth and metastasis.
conclusionBy stabilizing Zeb1 in cancer cells and delivering exosomes to induce M2 macrophage polarization, LINC00963 promoted the malignancy and metastasis of LUAD. Targeting LINC00963 may become a valuable therapeutic target for LUAD.
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