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Published on: April 28, 2021
Werner helicase is required for proliferation and DNA damage repair in multiple myeloma
Dilara Akcora-Yildiz1, Tulin Ozkan2, Mehmet Ozen3
1Department of Biology, Art & Science Faculty, Mehmet Akif Ersoy University, Burdur, Turkey. dilaraakcora@mehmetakif.edu.tr.
Background:
Multiple myeloma (MM), characterized by extensive genomic instability and aberrant DNA damage repair, is a plasma cell malignancy due to the excessive proliferation of monoclonal antibody-producing plasma cells in the bone marrow. Despite the significant improvement in the survival of patients with the development of novel therapeutic agents, MM remains an incurable disease. Werner (WRN) helicase, a member of the RecQ helicase family that contributes to DNA replication, recombination, and repair, has been highlighted in cancer cell survival, yet the role and mechanism of WRN in MM remain unclear.
Methods And Results:
Increased mRNA expression of WRN in newly diagnosed and relapsed CD138+ myeloma plasma cells than normal CD138+ plasma cells and their matched CD138- non-tumorigenic cells were detected by qPCR. Using NSC19630, a specific WRN helicase inhibitor, we further showed decreased cell viability, proliferation, and DNA repair and increased DNA damage and apoptosis in MM cells by MTT assay, cell cycle assay, apoptosis assay, and Western blotting.
Conclusions:
The results of the present study demonstrate that WRN is essential in MM cell viability, proliferation, and genomic stability, indicating its inhibition may enhance the efficacy of chemotherapy in MM.
Insights
Werner (WRN) helicase is crucial for multiple myeloma (MM) cell survival and genomic stability. Inhibiting WRN helicase significantly reduces MM cell viability and proliferation, suggesting a potential new therapeutic strategy for this incurable cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Multiple myeloma (MM) is a plasma cell malignancy characterized by genomic instability and DNA repair defects.
- Despite advances, MM remains incurable, highlighting the need for novel therapeutic targets.
- The role of Werner (WRN) helicase, involved in DNA repair and replication, in MM pathogenesis is not well understood.
Purpose of the Study:
- To investigate the role and mechanism of Werner (WRN) helicase in multiple myeloma.
- To evaluate the therapeutic potential of WRN inhibition in MM.
Main Methods:
- Quantitative PCR (qPCR) to measure WRN mRNA expression in myeloma cells.
- Inhibition of WRN helicase using NSC19630.
- MTT assay, cell cycle analysis, apoptosis assays, and Western blotting to assess cellular effects.
Main Results:
- Elevated WRN mRNA expression was observed in myeloma plasma cells compared to normal cells.
- WRN inhibition led to decreased cell viability, proliferation, and DNA repair.
- Inhibition also resulted in increased DNA damage and apoptosis in MM cells.
Conclusions:
- Werner (WRN) helicase is essential for MM cell viability, proliferation, and genomic stability.
- Targeting WRN helicase may represent a promising strategy to enhance chemotherapy efficacy in MM patients.
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