Identification of KDM4C as a gene conferring drug resistance in multiple myeloma

Na Zhang1,2, Ruilong Lan3, Yingyu Chen1

  • 1Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, 350001, China.

Open Life Sciences
|April 16, 2024
PubMed

Insights

This study identifies KDM4C as a key driver of bortezomib (BTZ) resistance in multiple myeloma (MM). Inhibiting KDM4C may restore sensitivity to BTZ, offering a new strategy for treating resistant MM patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Bortezomib (BTZ) is a crucial proteasome inhibitor for multiple myeloma (MM).
  • Drug resistance to BTZ leads to disease relapse and poor patient prognosis.
  • Identifying mechanisms of BTZ resistance is critical for improving MM treatment outcomes.

Purpose of the Study:

  • To identify novel genes contributing to BTZ resistance in multiple myeloma.
  • To investigate the functional role of identified genes in mediating BTZ resistance.
  • To explore KDM4C as a potential therapeutic target for overcoming BTZ resistance.

Main Methods:

  • Screening of 26 genes associated with drug resistance in MM cell lines.
  • Quantitative analysis of gene expression in BTZ-sensitive versus BTZ-resistant MM cells.
  • Functional studies involving KDM4C overexpression and knockdown (using shRNA) in MM cells.

Main Results:

  • KDM4C expression was significantly elevated in BTZ-resistant MM cells compared to sensitive cells.
  • Overexpression of KDM4C increased MM cell tolerance to BTZ.
  • Knockdown of KDM4C sensitized BTZ-resistant MM cells to BTZ treatment.

Conclusions:

  • KDM4C plays a critical role in conferring resistance to bortezomib in multiple myeloma.
  • KDM4C represents a promising therapeutic target for overcoming BTZ resistance in MM.
  • Targeting KDM4C could offer a novel strategy to improve treatment efficacy for relapsed or refractory MM.

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