HAS2 facilitates glioma cell malignancy and suppresses ferroptosis in an FZD7-dependent manner.

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  • Additional Information
    • Source:
      Publisher: Wiley Publishing on behalf of the Japanese Cancer Association Country of Publication: England NLM ID: 101168776 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1349-7006 (Electronic) Linking ISSN: 13479032 NLM ISO Abbreviation: Cancer Sci Subsets: MEDLINE
    • Publication Information:
      Publication: 2005- : Oxford : Wiley Publishing on behalf of the Japanese Cancer Association
      Original Publication: Tokyo : Japanese Cancer Association, c2003-
    • Subject Terms:
      Ferroptosis*/genetics ; Glioma*/pathology ; Glioma*/genetics ; Glioma*/metabolism ; Frizzled Receptors*/metabolism ; Frizzled Receptors*/genetics ; Hyaluronan Synthases*/metabolism ; Hyaluronan Synthases*/genetics ; Gene Expression Regulation, Neoplastic* ; Brain Neoplasms*/pathology ; Brain Neoplasms*/genetics ; Brain Neoplasms*/metabolism; Humans ; Cell Line, Tumor ; Animals ; Mice ; Prognosis ; Wnt Signaling Pathway/genetics ; Mice, Nude ; Male ; Female
    • Abstract:
      Glioma is the most common malignant tumor in the central nervous system, and it is crucial to uncover the factors that influence prognosis. In this study, we utilized Mfuzz to identify a gene set that showed a negative correlation with overall survival in patients with glioma. Gene Ontology (GO) enrichment analyses were then undertaken to gain insights into the functional characteristics and pathways associated with these genes. The expression distribution of Hyaluronan Synthase 2 (HAS2) was explored across multiple datasets, revealing its expression patterns. In vitro and in vivo experiments were carried out through gene knockdown and overexpression to validate the functionality of HAS2. Potential upstream transcription factors of HAS2 were predicted using transcriptional regulatory databases, and these predictions were experimentally validated using ChIP-PCR and dual-luciferase reporter gene assays. The results showed that elevated expression of HAS2 in glioma indicates poor prognosis. HAS2 was found to play a role in activating an antiferroptosis pathway in glioma cells. Inhibiting HAS2 significantly increased cellular sensitivity to ferroptosis-inducing agents. Finally, we determined that the oncogenic effect of HAS2 is mediated by the key receptor of the WNT pathway, FZD7.
      (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
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    • Grant Information:
      the Outstanding Young and Middle-aged Talents Support Program of the First Affiliated Hospital with Nanjing Medical University (Jiangsu Province Hospital); ZDXK202225 Jiangsu Province Capability Improvement Project through Science, Technology and Education
    • Contributed Indexing:
      Keywords: FZD7; HAS2; ferroptosis resistance; glioma; transcriptional regulation
    • Accession Number:
      0 (Frizzled Receptors)
      0 (FZD7 protein, human)
      EC 2.4.1.212 (Hyaluronan Synthases)
      EC 2.4.1.212 (HAS2 protein, human)
    • Publication Date:
      Date Created: 20240530 Date Completed: 20240808 Latest Revision: 20240918
    • Publication Date:
      20240918
    • Accession Number:
      PMC11309948
    • Accession Number:
      10.1111/cas.16232
    • Accession Number:
      38816349