Exosomal transfer of miR-769-5p promotes osteosarcoma proliferation and metastasis by targeting DUSP16.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34663350", "kind": "science-record", "revision": 5, "content_hash": "sha256:cf72403766e42019c9440afb57f64e1f78f30c5adbe3b14660193bca9369244e", "created_at": "2026-11-01T17:36:19Z", "updated_at": "2026-11-01T22:47:44Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Exosomal transfer of miR-769-5p promotes osteosarcoma proliferation and metastasis by targeting DUSP16.", "doi": "10.1186/s12935-021-02257-4", "pmid": "34663350", "authors": ["Wanshun Liu", "Binyu Wang", "Ao Duan", "Kai Shen", "Qi Zhang", "Xiaolu Tang", "Yongzhong Wei", "Jian Tang", "Sheng Zhang"], "journal": "Cancer cell international", "year": 2021, "abstract": "BACKGROUND: Osteosarcoma (OS) is a malignant tumor originating from mesenchymal stem cells, and has an extremely high fatality rate and ability to metastasize. Although mounting evidence suggests that miR-769-5p is strongly associated with the malignant progression and poor prognosis of various tumors, the exact role of miR-769-5p in OS is still unclear. Therefore, this study aimed to explore the relationship between miR-769-5p and the malignant progression of OS, and its underlying mechanism of action.\nMETHODS: miR-769-5p expression was analyzed in GSE28423 from the GEO database and measured in OS clinical specimens and cell lines. The effects of miR-769-5p on OS proliferation, migration and invasion were measured both in vivo and in vitro. In addition, bioinformatics analyses and luciferase reporter assays were used to explore the target genes of miR-769-5p. Rescue experiments were also conducted. Moreover, a co-culture model was used to test the cell interaction between bone mesenchymal stem cells (BMSC) and OS cells.\nRESULTS: We found that miR-769-5p is highly expressed in OS clinical specimens and cell lines. In vivo and in vitro experiments also showed that miR-769-5p significantly promoted the proliferation, migration and invasion of OS cells. Dual-specific phosphatase 16 (DUSP16) was negatively associated with miR-769-5p expression in OS cells and tissue samples and was validated as the downstream target by luciferase reporter assay and western blotting. Rescue experiments showed that DUSP16 reverses the effect of miR-769-5p on OS cells by negatively regulating the JNK/p38 MAPK signaling pathway. Additionally, the results of the co-culture of BMSCs and OS cells confirmed that miR-769-5p was transferred from BMSCs to OS cells through exosomes.\nCONCLUSIONS: In summary, this study demonstrates for the first time that BMSC-derived exosomal miR-769-5p promotes OS proliferation and metastasis by targeting DUSP16 and activating the JNK/p38 MAPK signaling pathway, which could provide rationale for a new therapeutic strategy for OS.", "claims": [{"id": "claim-method", "statement": "Comparisons between two groups were analyzed by student’s t-test, while those among multiple groups were examined by one-way ANOVA.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34663350", "locator": "sections[19] \"Statistical analysis\" paragraph 2", "quote": "Comparisons between two groups were analyzed by student’s t-test, while those among multiple groups were examined by one-way ANOVA."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Most of the datasets supporting the conclusions of this article are included within this article and the additional files. The datasets used or analyzed during the current study are available on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34663350", "locator": "sections[38] \"Availability of data and materials\" paragraph 2", "quote": "Most of the datasets supporting the conclusions of this article are included within this article and the additional files. The datasets used or analyzed during the current study are available on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "In summary, this study demonstrates for the first time that BMSC-derived exosomal miR-769-5p promotes OS proliferation and metastasis by targeting DUSP16 and activating the JNK/p38 MAPK signaling pathway, which could provide rationale for a new therapeutic strategy for OS.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34663350", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "In summary, this study demonstrates for the first time that BMSC-derived exosomal miR-769-5p promotes OS proliferation and metastasis by targeting DUSP16 and activating the JNK/p38 MAPK signaling pathway, which could provide rationale for a new therapeutic strategy for OS."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "In summary, this study demonstrates for the first time that BMSC-derived exosomal miR-769-5p promotes OS proliferation and metastasis by targeting DUSP16 and activating the JNK/p38 MAPK signaling pathway, which could provide rationale for a new therapeutic strategy for OS.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:34663350"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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In addition, bioinformatics an", "sed in OS clinical specimens and cell lines. In vivo and in vitro experiments also showed that mi", "r 20 six-week-old female BALB/c athymic nude mice were randomly divided into four groups (MG63-miR", "bcutaneous tumor formation experiments. Nude mice were injected with luciferase-expressing stably t"], "order_basis": "paper_text_order:789", "id": "assay:1"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ream target by luciferase reporter assay and western blotting. Rescue experiments showed that DUSP16 rever"], "order_basis": "paper_text_order:1528", "id": "assay:2"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["s (CBTCCCAS, Shanghai, China). OS cells were cultured in DMEM (Gibco, CA, USA) containing 10% fetal b", "33.5 °C. BMSCs purchased from CBTCCCAS were cultured in DMEM (Gibco) containing 10% FBS (Gibco, NY)", "and human OS cells (HOS, MG63, 143B, Saos-2, U2OS) were provided by Cell Bank of Type Culture"], "order_basis": "paper_text_order:2246", "id": "assay:3"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["e injected with luciferase-expressing stably transfected OS cells in 200 μl OS cell suspension (2 × 1", "e injected with luciferase-expressing stably transfected OS cells (2 × 107/ml, 100 µl) via the tail v"], "order_basis": "paper_text_order:3103", "id": "assay:4"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["d the tumors were dissected for weighing and IHC. 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