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Updated: Jun 24, 2025

Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
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Published on: October 4, 2019

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Tumour microenvironment programming by an RNA-RNA-binding protein complex creates a druggable vulnerability in

Lele Wu1, Zheng Zhao2, Yong Jae Shin3

  • 1Laboratory of NFκB Signalling, Institute of Molecular and Cell Biology (IMCB), Agency for Science Technology and Research (A*STAR), Singapore, Republic of Singapore.

Nature Cell Biology
|June 10, 2024
PubMed

Insights

Targeting the LOC-DHX15 complex with small molecules can overcome treatment resistance in IDH-wild-type glioblastomas by disrupting cancer-immune cell communication and improving survival rates.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • IDH-wild-type glioblastomas exhibit poor prognoses and limited treatment efficacy.
  • Tumor growth and resistance are driven by glioma-associated microglia and macrophages (GAMs).
  • The RNA-RNA-binding protein complex LOC-DHX15 mediates cancer-immune cell crosstalk.

Purpose of the Study:

  • To investigate the role of the LOC-DHX15 complex in glioblastoma progression.
  • To evaluate the therapeutic potential of targeting LOC-DHX15.

Main Methods:

  • Investigated the LOC-DHX15 complex in glioblastoma models.
  • Utilized blood-brain barrier-permeable small molecules to target the complex.
  • Assessed effects on immune cell infiltration, tumor growth, and cancer cell properties.

Main Results:

  • The LOC-DHX15 complex promotes tumor growth and immune cell infiltration.
  • Targeting LOC-DHX15 with small molecules disrupted cancer-immune cell communication.
  • Therapeutic intervention impeded glioblastoma cell survival and stem-like characteristics.

Conclusions:

  • The LOC-DHX15 complex is a critical driver of glioblastoma aggressiveness.
  • Targeting RNA-RNA-binding protein interactions offers a promising therapeutic strategy for glioblastomas.
  • This approach may have broader applications in treating other cancers and diseases.

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