MicroRNA-409-5p Inhibits GIST Tumorigenesis and Improves Imatinib Resistance by Targeting KDM4D Expression

Cheng Qiu1, Yong-Dong Feng1, Xi Yang2

  • 1GI Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Current Medical Science
|October 12, 2023
PubMed
Abstract

Insights

MicroRNA-409-5p inhibits gastrointestinal stromal tumor (GIST) growth by targeting KDM4D, reducing angiogenesis. This pathway offers a new strategy for treating imatinib-resistant GIST.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Gastrointestinal stromal tumors (GISTs) exhibit rapid proliferation driven by angiogenesis.
  • MicroRNAs (miRNAs) are implicated in the progression of tumor angiogenesis.
  • Understanding specific miRNA mechanisms in GIST is crucial for therapeutic development.

Purpose of the Study:

  • To elucidate the role of microRNA-409-5p (miR-409-5p) in GIST development and angiogenesis.
  • To identify the molecular targets and signaling pathways influenced by miR-409-5p in GIST cells.

Main Methods:

  • Comparative analysis of miR-409-5p expression in GIST tissues versus adjacent tissues.
  • Prediction and validation of miR-409-5p target genes.
  • Functional studies in GIST cell lines (GIST-T1, GIST882) using lentiviral transfection.
  • Assessment of angiogenesis-related protein expression via Western blotting and ELISA.

Main Results:

  • miR-409-5p expression was significantly decreased in GIST tissues.
  • Upregulation of miR-409-5p inhibited hypoxia-inducible transcription factor 1β (HIF1β) and vascular endothelial growth factor A (VEGF-A) protein levels.
  • miR-409-5p directly targets Lysine-specific demethylase 4D (KDM4D) mRNA, inhibiting angiogenesis.
  • Combination therapy of miR-409-5p and imatinib enhanced anti-angiogenic effects.

Conclusions:

  • The miR-409-5p/KDM4D/HIF1β/VEGF-A pathway is a novel mechanism in GIST angiogenesis.
  • This pathway represents a potential therapeutic target for overcoming imatinib resistance in GIST.

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