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Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
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RPN2 is targeted by miR-181c and mediates glioma progression and temozolomide sensitivity via the wnt/β-catenin

Jikui Sun1,2, Quanfeng Ma2, Banban Li3

  • 1School of Medicine, Nankai University, 94 Weijin Road, Tianjin, 300071, China.

Cell Death & Disease
|October 22, 2020
PubMed

Insights

Researchers identified a new signaling pathway involving miR-181c and RPN2 that drives glioma development and resistance to temozolomide (TMZ). Targeting this axis could offer new therapeutic strategies for glioblastoma (GBM).

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNAs (miRNAs) and messenger RNAs (mRNAs) regulate cancer signaling pathways critical for glioma.
  • Dysregulation of these networks contributes to glioma initiation and progression.

Purpose of the Study:

  • To investigate the role of RPN2 in glioma and its relationship with microRNA-181c (miR-181c).
  • To elucidate the underlying molecular mechanisms of RPN2 in glioma tumorigenesis and temozolomide (TMZ) resistance.

Main Methods:

  • Bioinformatics analysis and experimental validation in glioma specimens.
  • In vitro and in vivo studies involving RPN2 knockdown and miR-181c expression.
  • Analysis of the Wnt/β-catenin signaling pathway and its components.

Main Results:

  • RPN2 was significantly upregulated in glioma tissues and correlated with higher WHO grade and poorer prognosis.
  • RPN2 knockdown suppressed glioma cell proliferation, invasion, and apoptosis, while enhancing TMZ sensitivity.
  • RPN2 was identified as a direct target of miR-181c, and the miR-181c/RPN2 axis modulated Wnt/β-catenin signaling and TMZ resistance.

Conclusions:

  • A novel miR-181c/RPN2/Wnt/β-catenin signaling axis was identified in glioma.
  • This axis plays a crucial role in glioma tumorigenesis and TMZ resistance.
  • The miR-181c/RPN2 axis represents a potential therapeutic target for glioblastoma (GBM).

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