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MSI2-TGF-β/TGF-β R1/SMAD3 positive feedback regulation in glioblastoma

Xingjun Jiang1, Jun Tan2, Yin Wen2

  • 1Department of Neurosurgery, Collaborative Innovation Center for Cancer Medicine, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, Hunan, People's Republic of China. jiangxingjun@sina.com.

Cancer Chemotherapy and Pharmacology
|June 29, 2019
PubMed
Abstract

Insights

Musashi RNA-binding protein 2 (MSI2) drives glioblastoma chemoresistance by activating epithelial-to-mesenchymal transition and MGMT expression. Targeting MSI2 may offer a new therapeutic strategy for glioblastoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Glioblastoma is a highly aggressive brain tumor known for its resistance to chemotherapy and inevitable relapse.
  • The precise molecular mechanisms underlying glioblastoma chemoresistance are not fully understood, necessitating further investigation.

Purpose of the Study:

  • To explore the molecular and cellular mechanisms contributing to chemoresistance in glioblastoma.
  • To investigate the role of Musashi RNA-binding protein 2 (MSI2) in glioblastoma chemoresistance.

Main Methods:

  • Assessed MSI2 expression in glioblastoma tissues and cells.
  • Evaluated the impact of MSI2 on epithelial-to-mesenchymal transition (EMT), temozolomide (TMZ) resistance, invasion, migration, and proliferation.
  • Investigated the signaling pathways regulated by MSI2, including TGFβ R1/SMAD3 and its effect on O6-methylguanine-DNA methyltransferase (MGMT).

Main Results:

  • Elevated MSI2 expression was detected in glioblastoma tissues.
  • MSI2 modulation significantly influenced glioblastoma cell invasion, migration, and proliferation.
  • Silencing MSI2 inhibited tumor growth, reduced MGMT expression, and reversed TMZ resistance in vivo, while activating Snail and TGFβ R1/SMAD3 signaling.

Conclusions:

  • A positive feedback loop involving MSI2, TGFβ/SMAD3 signaling, EMT, and MGMT contributes to glioblastoma chemoresistance.
  • MSI2 represents a potential therapeutic target for overcoming chemoresistance in glioblastoma.
Keywords:
ChemoresistanceEpithelial-to-mesenchymal transitionGlioblastomaGliomaSMAD3TGFβ

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