Werner helicase is required for proliferation and DNA damage repair in multiple myeloma.
DNA repair
Genomic stability
Multiple myeloma
NSC 19630
Werner helicase
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
Feb 2023
Feb 2023
Historique:
received:
01
08
2022
accepted:
06
12
2022
pubmed:
15
12
2022
medline:
3
2
2023
entrez:
14
12
2022
Statut:
ppublish
Résumé
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.
Sections du résumé
BACKGROUND
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
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
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.
Identifiants
pubmed: 36515823
doi: 10.1007/s11033-022-08178-3
pii: 10.1007/s11033-022-08178-3
doi:
Substances chimiques
Werner Syndrome Helicase
EC 3.6.4.12
Exodeoxyribonucleases
EC 3.1.-
RecQ Helicases
EC 3.6.4.12
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1565-1573Subventions
Organisme : Türkiye Bilimsel ve Teknolojik Araştirma Kurumu
ID : 113Z383
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature B.V.
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