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Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
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miR-433 Inhibits Glioblastoma Progression by Suppressing the PI3K/Akt Signaling Pathway Through Direct Targeting of

Huawei Jiang1, Zhiwei Su2, Wangxiong Hu3

  • 1Department of Hematology (Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Omics : a Journal of Integrative Biology
|May 17, 2023
PubMed

Insights

MicroRNA-433 (miR-433) acts as a tumor suppressor in glioblastoma multiforme (GBM). Lower miR-433 levels correlate with reduced survival, and its upregulation inhibits GBM growth and spread, suggesting it as a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Glioblastoma multiforme (GBM) is an aggressive brain tumor requiring novel biomarkers and therapeutic targets.
  • MicroRNA-433 (miR-433) has shown tumor-suppressive roles in various cancers, but its function in GBM remains largely unexplored.

Purpose of the Study:

  • To investigate the role and underlying mechanisms of miR-433 in glioblastoma.
  • To determine if miR-433 can serve as a potential therapeutic target for GBM.

Main Methods:

  • Analysis of miR-433 expression in 198 glioma patients from The Cancer Genome Atlas (TCGA).
  • In vitro studies using glioma cell lines (LN229, T98G) to assess proliferation, migration, and invasion.
  • In vivo mouse models to evaluate tumor growth inhibition.
  • Identification of miR-433 direct targets and pathway analysis (ERBB4, PI3K/Akt).

Main Results:

  • Decreased miR-433 expression was observed in glioma, significantly associated with shorter overall survival.
  • Overexpression of miR-433 suppressed glioma cell proliferation, migration, and invasion in vitro.
  • Upregulation of miR-433 inhibited glioma tumor growth in vivo.
  • ERBB4 was identified as a direct target of miR-433, and its overexpression rescued miR-433's effects.
  • miR-433 was found to suppress the PI3K/Akt pathway in glioma cells.

Conclusions:

  • miR-433 functions as a tumor suppressor in glioblastoma.
  • miR-433 exhibits potential as a therapeutic target for GBM.
  • Further research is needed for clinical translation of miR-433-based therapies for GBM.
Keywords:
ERBB4PI3K/Akt signaling pathwaycancer researchdrug targetsglioblastomamiR-433

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