ArticleCancer management and research2019
Overexpression of Notch3 is associated with metastasis and poor prognosis in osteosarcoma patients.
Article in Cancer management and research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 34 citations in OpenAlex.
- Targeting developmental vulnerabilities in childhood sarcomas.Cancer metastasis reviews · 2025Review
- Review
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- Cellular senescence-driven transcriptional reprogramming of theGenes & diseases · 2024Article
- Shikonin suppresses proliferation of osteosarcoma cells by inducing ferroptosis through promoting Nrf2 ubiquitination and inhibiting the xCT/GPX4 regulatory axis.Frontiers in pharmacology · 2024Article
- Article
- LIN28B promotes cell invasion and colorectal cancer metastasis via CLDN1 and NOTCH3.JCI insight · 2023Article
- Deciphering the Signaling Mechanisms of Osteosarcoma Tumorigenesis.International journal of molecular sciences · 2023Review
- NOTCH Signaling in Osteosarcoma.Current issues in molecular biology · 2023Review
- Regulation of Hepatocytes in G0 and G1 Phases by NOTCH3 mRNA, miR-369-3p, and rno-Rmdn2_0006 during the Initial Stage of Rat Liver Regeneration.Genetics research · 2023Article
- Identification of therapeutic targets for osteosarcoma by integrating single-cell RNA sequencing and network pharmacology.Frontiers in pharmacology · 2022Article
- Association of Septic Shock with Mortality in Hospitalized COVID-19 Patients in Wuhan, China.Advances in virology · 2022Article
- LncRNA UCA1 accelerates osteosarcoma progression via miR-145 and Wnt/β-catenin pathway.American journal of translational research · 2022Article
- Lung Adenocarcinoma Cells Promote Self-Migration and Self-Invasion by Activating Neutrophils to Upregulate Notch3 Expression of Cancer Cells.Frontiers in molecular biosciences · 2021Article
- Development of a tRNA-Derived Small RNA Prognostic Panel and Their Potential Functions in Osteosarcoma.Frontiers in oncology · 2021Article
- The Role of Notch3 Signaling in Cancer Stemness and Chemoresistance: Molecular Mechanisms and Targeting Strategies.Frontiers in molecular biosciences · 2021Review
- Magnetic transfection with superparamagnetic chitosan-loaded IGFBPRoyal Society open science · 2021Article
- Notch-1 promotes the malignant progression of osteosarcoma through the activation of cell division cycle 20.Aging · 2020Article
- Article
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8 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundNotch signaling abnormalities are associated with the development of various tumors, including hematopoietic and epithelium-derived tumors. However, the role of Notch signaling in tumors originating from mesenchymal cells is unclear. The effect of Notch3 expression on the prognosis of osteosarcoma and its role and mechanism in osteosarcoma cells have never been reported. MATERIALS AND
methodsIn this study, we performed a clinicopathological analysis of 70 cases of osteosarcoma, with primary focus on survival. Osteosarcoma cell lines MTH and U2OS were used. After knockdown of Notch3 by lentiviral transfection and siRNA, the cell cycle, cell viability, and wound healing capacity were assessed. Subsequently, the Transwell assay was performed, and the expression levels of hairy and enhancer of split-1 (Hes1) and matrix metalloproteinase 7 (MMP7) were detected by RT-PCR and Western blot assay. The expression of MMP7 was also detected after knockdown of Hes1. Animal experiments were performed by injecting the cell lines MTH of Notch3 knockdown into mice tail veins and comparing the development of lung metastasis with the control group.
resultsComparison of survival curves showed that Notch3 expression significantly impacts patient survival. Additionally, multivariate analysis revealed that Notch3 is an independent prognostic factor for osteosarcoma. In in vivo experiments, osteosarcoma-associated pulmonary metastasis in nude mice was reduced after Notch3 silencing. The expression of downstream effector molecule, Hes1, and that of the invasion and metastasis-associated proteolytic enzyme, MMP7, were reduced, and MMP7 was further decreased by Hes1 knockdown in in vitro experiments.
conclusionNotch3 is a prognostic factor for osteosarcoma and might regulate its invasion and metastasis through the downstream target gene
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