Related Experiment Video
Updated: Jun 28, 2025

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
Published on: January 7, 2019
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.
Abstract:
Bortezomib (BTZ), a proteasome inhibitor, is a promising therapeutic option for multiple myeloma (MM) patients. However, drug resistance often occurs, leading to disease relapse and poor prognosis. In this study, we aimed to identify novel genes associated with drug resistance and investigate their roles in BTZ resistance. Through the screening of 26 genes frequently associated with chemosensitivity or drug resistance, we discovered that KDM4C, a histone demethylase, exhibited increased expression in BTZ-resistant MM cells compared to their sensitive counterparts. Overexpression of KDM4C enhanced the tolerance of a MM cell line to the drug, whereas the knockdown of KDM4C, using shRNA, increased the sensitivity of resistant cells to BTZ treatment. This suggests that KDM4C plays a pivotal role in conferring BTZ resistance. Our study offers fresh insights into BTZ resistance in MM and highlights KDM4C as a potential target for overcoming drug resistance.
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.
Related Concept Videos
Treatment Resistant Cancers
Inhibition of Cdk Activity
Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...

