Knockdown of circHIPK3 Facilitates Temozolomide Sensitivity in Glioma by Regulating Cellular Behaviors Through miR-524-5p/KIF2A-Mediated PI3K/AKT Pathway.

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  • Author(s): Yin H;Yin H; Cui X; Cui X
  • Source:
    Cancer biotherapy & radiopharmaceuticals [Cancer Biother Radiopharm] 2021 Sep; Vol. 36 (7), pp. 556-567. Date of Electronic Publication: 2020 Aug 21.
  • Publication Type:
    Journal Article
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Mary Ann Liebert, Inc Country of Publication: United States NLM ID: 9605408 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-8852 (Electronic) Linking ISSN: 10849785 NLM ISO Abbreviation: Cancer Biother Radiopharm Subsets: MEDLINE
    • Publication Information:
      Original Publication: Larchmont, NY : Mary Ann Liebert, Inc., c1996-
    • Subject Terms:
      Brain Neoplasms/*drug therapy ; Glioma/*drug therapy ; Kinesins/*metabolism ; MicroRNAs/*metabolism ; Phosphatidylinositol 3-Kinase/*metabolism ; Proto-Oncogene Proteins c-akt/*metabolism ; RNA, Circular/*genetics ; Temozolomide/*pharmacology; Antineoplastic Agents, Alkylating/pharmacology ; Brain Neoplasms/genetics ; Brain Neoplasms/metabolism ; Brain Neoplasms/pathology ; Cell Line, Tumor ; Glioma/genetics ; Glioma/metabolism ; Glioma/pathology ; Humans ; Kinesins/genetics ; MicroRNAs/genetics ; RNA, Circular/metabolism
    • Abstract:
      Background: Temozolomide (TMZ) resistance is a serious hindrance in clinical chemotherapy for glioma. Circular RNA homeodomain interacting protein kinase 3 (circHIPK3) can be involved in regulating the progression of glioma, but the molecular mechanism of circHIPK3 in TMZ-resistant-glioma is completely unclear. Materials and Methods: The levels of circRNA, miRNA, and mRNA were examined using quantitative real-time polymerase chain reaction. 3-(4,5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide assay was used for assessing the half inhibitory concentration (IC 50 ) of TMZ and cell proliferation. Cell apoptosis and metastasis (migration and invasion) were detected by flow cytometry and transwell assay, respectively. Western blot and dual-luciferase reporter assay were performed several times to analyze the expression levels of associated proteins and the targeted relation. Results: The upregulation of circHIPK3 was found in TMZ-resistant glioma tissues and cells. Both circHIPK3 knockdown and kinesin family member 2A (KIF2A) inhibition could facilitate TMZ sensitivity and apoptosis but repress proliferation and metastasis in TMZ-resistant glioma cells. CircHIPK3 targeted microRNA-524-5p (miR-524-5p) and KIF2A functioned as a downstream target of miR-524-5p. Decrease of miR-524-5p relieved the effects of si-circHIPK3 on TMZ-resistant glioma cells by upregulating KIF2A. Downregulation of circHIPK3 refrained the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signal pathway partly through miR-524-5p/KIF2A axis. Conclusions : Knockdown of circHIPK3 promoted TMZ sensitivity in glioma by modulating proliferation, metastasis, and apoptosis through miR-524-5p/KIF2A-mediated PI3K/AKT pathway. CircHIPK3 may be the potential target for the diagnosis and therapy of TMZ-resistant glioma.
    • Contributed Indexing:
      Keywords: KIF2A; PI3K/AKT pathway; circHIPK3; glioma; miR-524-5p; temozolomide
    • Accession Number:
      0 (Antineoplastic Agents, Alkylating)
      0 (KIF2A protein, human)
      0 (MIRN-524 microRNA, human)
      0 (MicroRNAs)
      0 (RNA, Circular)
      EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
      EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
      EC 3.6.4.4 (Kinesins)
      YF1K15M17Y (Temozolomide)
    • Publication Date:
      Date Created: 20200825 Date Completed: 20220128 Latest Revision: 20220128
    • Publication Date:
      20240105
    • Accession Number:
      10.1089/cbr.2020.3575
    • Accession Number:
      32833501