ArticleJournal of translational medicine2025
HMGCL activates autophagy in osteosarcoma through β-HB mediated inhibition of the PI3K/AKT/mTOR signaling pathway.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Decoding osteosarcoma pathogenesis: the pivotal influence of mEpigenetics · 2026Review
- Acetoacetate-GPR43 axis epigenetically silences IL-6/CSF1 to restrict TAMs-driven metastatic lung cancer.Journal of translational medicine · 2026Article
- Ginsenoside Rg3 attenuates fatigue by restoring autophagic homeostasis via the PI3K/AKT/mTOR pathway in ammonium chloride-induced C2C12 cells.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Comparative chromatin accessibility and transcriptome analyses identify key energy metabolism genes for hypoxia adaptation in embryos of Tibetan chickens.Poultry science · 2026Article
- Current Understanding of Bovine Ketosis: From Molecular Basis to Farm-Level Management.Animals : an open access journal from MDPI · 2025Review
- TRIM17 promotes the progression of osteosarcoma by regulating PDK1 m6A modification-mediated AKT/mTOR pathway activation through ubiquitination of FTO.Cell death & disease · 2025Article
- Research status and prospects of molecular pathological mechanisms and novel therapeutic targets of osteosarcoma: a systematic review.Frontiers in oncology · 2025Review
- The paradoxical role of stem cells in osteosarcoma: from pathogenesis to therapeutic breakthroughs.Frontiers in oncology · 2025Review
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8 authors.
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Abstract
background3-hydroxy-3-methylglutaryl-coenzymOHBe A(HMG-CoA) lyase (HMGCL) catalyzes the cleavage of HMG-CoA into acetyl-CoA and acetoacetic acid and serves as a rate-limiting enzyme in the metabolism of ketone bodies. While HMGCL is involved in various biological processes, its specific role in osteosarcoma remains unclear.
methodsUsing data from a public database of osteosarcoma patients, we investigated the expression and prognostic value of HMGCL. The effects of HMGCL on the proliferation, migration, and invasion of osteosarcoma cells were assessed using CCK-8 assays, wound healing tests, and transwell invasion assays. We explored and validated the specific molecular mechanisms by which HMGCL influences osteosarcoma through transcriptome sequencing. Finally, we established a subcutaneous tumor formation model in nude mice to investigate the function of HMGCL in vivo.
resultsThe expression of HMGCL is downregulated in osteosarcoma and correlates with the prognosis of osteosarcoma patients. Overexpression of HMGCL can inhibit the proliferation, migration, and invasion of osteosarcoma cells, as well as tumor growth in vivo. Through our investigation of the underlying mechanism, we found that HMGCL may inhibit the activation of the PI3K/AKT/mTOR signaling pathway via its product, β-HB. This inhibition promotes the phosphorylation of ULK1, thereby facilitating autophagy in osteosarcoma cells and enhancing the malignancy of the disease.
conclusionHMGCL inhibits the activation of the PI3K/AKT/mTOR signaling pathway mediated by β-HB, thereby reducing the proliferation, migration, and invasion of osteosarcoma cells while promoting autophagy. HMGCL may represent a new target for the treatment of osteosarcoma, offering new hope for patients with this disease.
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