ArticleMolecular medicine (Cambridge, Mass.)2023
RILP inhibits tumor progression in osteosarcoma via Grb10-mediated inhibition of the PI3K/AKT/mTOR pathway.
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 21 papers.
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21 citing papers in PubMed, 25 citations in OpenAlex.
- Adaptor protein CIN85 potentiates the motility of osteosarcoma cells via the Akt/mTOR and MMP2-COL3A1 axis.Molecular oncology · 2026Article
- Veratramine influences the proliferation of human osteosarcoma cells through modulating the PI3K/AKT signaling cascade.Genes & diseases · 2026Article
- AnCurrent medicinal chemistry · 2026Article
- GRB10 as a pan-cancer biomarker linking oncogenic signaling, immunosuppression, and immunotherapy resistance.Discover oncology · 2025Article
- 5'tiRNA-Glu-TTC targets TRPV3 and activates the PI3K/AKT signaling pathway to modulate skin photoaging.Non-coding RNA research · 2025Article
- Bibliometric analysis of autophagy in the diagnosis and treatment of osteosarcoma: a bibliometric analysis (2007-2023).Cancer biology & therapy · 2025Article
- HMGB1 and Its Signaling Pathway in Osteosarcoma: Current Advances in Targeted Therapy.Current issues in molecular biology · 2025Review
- Phosphatidylinositol 3-kinase and mechanistic target of rapamycin dualinhibitor, VDC597, as a therapeutic agent for canine osteosarcoma.The Journal of pharmacology and experimental therapeutics · 2025Article
- PiRNA hsa_pir_018849 promotes the proliferation and invasion of osteosarcoma cells by regulating the stability of CCN5 mRNA.Journal of orthopaedic surgery and research · 2025Article
- Harnessing multi‑omics to revolutionize understanding and management of osteosarcoma: A pathway to precision medicine (Review).International journal of molecular medicine · 2025Review
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- WNT inhibitor SP5-mediated SERPING1 suppresses lung adenocarcinoma progression via TSC2/mTOR pathway.Cell death & disease · 2025Article
- Using β-Elemene to reduce stemness and drug resistance in osteosarcoma: A focus on the AKT/FOXO1 signaling pathway and immune modulation.Journal of bone oncology · 2025Article
- Research status and prospects of molecular pathological mechanisms and novel therapeutic targets of osteosarcoma: a systematic review.Frontiers in oncology · 2025Review
- Synergistic effects of bloom helicase (BLM) inhibitor AO/854 with cisplatin in prostate cancer.Scientific reports · 2024Article
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- Article
- The role of programmed cell death in osteosarcoma: From pathogenesis to therapy.Cancer medicine · 2024Review
- Review
- Mechanism of mTOR/RILP-regulated autophagic flux in increased susceptibility to myocardial ischemia-reperfusion in diabetic mice.Frontiers in pharmacology · 2024Article
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5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRab-interacting lysosomal protein (RILP) contains an alpha-helical coil with an unexplored biological function in osteosarcoma. This study investigated the expression of RILP in osteosarcoma cells and tissues to determine the effect of RILP on the biological behaviors of osteosarcoma cells and the underlying mechanism.
methodsTumor Immune Estimation Resource (TIMER) database, The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database were used for bioinformatic analysis. Co-immunoprecipitation experiment was used to determine whether the two proteins were interacting. In functional tests, cell counting kit-8 (CCK-8) assay, colony formation assay, wound healing assay, transwell invasion assay, Immunofluorescence (IF) assay and immunohistochemical (IHC) assay were performed.
resultsOverexpression of RILP significantly inhibited proliferation and impaired metastasis ability of osteosarcoma cells, while silencing of RILP showed the opposite trend. RNA-seq data analysis was applied in 143B cells and pathway enrichment analysis revealed that differentially expressed genes were mainly enriched in the PI3K/AKT pathway. We further verified that overexpression of RILP restrained the PI3K/AKT/mTOR signaling pathway and induced autophagy in osteosarcoma cells, while the opposite trend was observed when PI3K pathway activator 740Y-P was used. 3-Methyladenine (3-MA), a selective autophagy inhibitor, partially attenuated the inhibitory effect of RILP on the migration and invasion ability of osteosarcoma cells, suggesting the involvement of autophagy in epithelial-mesenchymal transition regulation in osteosarcoma cells. Growth factor receptor binding protein-10 (Grb10), an adaptor protein, was confirmed as a potential target of RILP to restrain the PI3K/AKT signaling pathway. We subcutaneously injected stably overexpressing 143B osteosarcoma cells into nude mice and observed that overexpression of RILP inhibited tumor growth by inhibiting the PI3K/AKT/mTOR pathway.
conclusionOur study revealed that the expression of RILP was associated with favorable prognosis of osteosarcoma and RILP inhibits proliferation, migration, and invasion and promotes autophagy in osteosarcoma cells via Grb10-mediated inhibition of the PI3K/AKT/mTOR signaling pathway. In the future, targeting RILP may be a potential strategy for osteosarcoma treatment.
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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.