Werner helicase is required for proliferation and DNA damage repair in multiple myeloma

Abstract

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. 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. 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.