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Updated: Aug 12, 2025

Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
08:07

Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma

Published on: April 12, 2019

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Vitamin D inhibits osteosarcoma by reprogramming nonsense-mediated RNA decay and SNAI2-mediated

Enrico Capobianco, Vanessa McGaughey, Gerbenn Seraphin

    Biorxiv : the Preprint Server for Biology
    |January 30, 2023
    PubMed

    Insights

    Vitamin D inhibits osteosarcoma metastasis by targeting nonsense-mediated RNA decay (NMD), reactive oxygen species (ROS), and epithelial-to-mesenchymal transition (EMT). The active form, 1,25(OH)2D, and calcipotriol suppress tumor growth and metastasis.

    Area of Science:

    • Oncology
    • Endocrinology
    • Molecular Biology

    Background:

    • Osteosarcomas are aggressive, metastatic cancers resistant to immune responses.
    • Elevated nonsense-mediated RNA decay (NMD), reactive oxygen species (ROS), and epithelial-to-mesenchymal transition (EMT) contribute to osteosarcoma's malignancy.
    • The anti-cancer potential of vitamin D in osteosarcoma remains largely uncharacterized.

    Approach:

    • Investigated the impact of vitamin D and its receptor (VDR) on the NMD-ROS-EMT axis in vitro and in vivo.
    • Utilized 1,25(OH)2D, the active vitamin D metabolite, and epigenome-wide analysis.
    • Employed mouse xenograft metastasis models and siRNA knockdown of SNAI2.

    Key Points:

    • VDR signaling initially promotes EMT genes, but 1,25(OH)2D subsequently inhibits EMT by downregulating SNAI2.
    • VDR integrates with NMD pathways, autoregulating NMD machinery and upregulating anti-oncogenic NMD targets.
    • Vitamin D enhances antioxidative responses via SOD2 and suppresses ROS, sensitizing cells to its effects.

    Conclusions:

    • Vitamin D and its derivative calcipotriol exhibit potent anti-osteosarcoma effects, inhibiting metastasis and tumor growth.
    • Novel mechanisms involving NMD, ROS, and EMT pathways elucidate vitamin D's anti-cancer action.
    • Findings suggest therapeutic potential for vitamin D derivatives in treating osteosarcoma patients.

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