1. Activation-Induced Cytidine Deaminase Promotes Proliferation and Enhances Chemoresistance and Migration in B-cell Lymphoma
- Author
-
Shaheen Mowla, Grant Godsmark, and Leonardo Alves de Souza Rios
- Subjects
Cancer Research ,Programmed cell death ,Lymphoma, B-Cell ,medicine.medical_treatment ,Gene Expression ,Antineoplastic Agents ,Ectopic Gene Expression ,Targeted therapy ,Cell Movement ,Cell Line, Tumor ,Cytidine Deaminase ,medicine ,Activation-induced (cytidine) deaminase ,Animals ,Humans ,B-cell lymphoma ,Cell Proliferation ,biology ,Cell growth ,General Medicine ,Cytidine deaminase ,medicine.disease ,Burkitt Lymphoma ,Lymphoma ,Enzyme Activation ,Oncology ,Doxorubicin ,Drug Resistance, Neoplasm ,Gene Knockdown Techniques ,biology.protein ,Cancer research ,Ectopic expression ,DNA Damage - Abstract
Background/aim Activation-induced cytidine deaminase (AID) is a DNA modifying enzyme which has an essential function in promoting antibody diversification. Its overexpression is strongly associated with B-cell derived malignancies including Burkitt lymphoma, where AID is required for the characteristic c-MYC/IGH translocation. This study aimed at defining AID's oncopathogenic role which is still poorly understood. Materials and methods We created over-expressing and knock-down cell culture models of AID, and used cellular assays to provide insight into its contribution to lymphomagenesis. Results We showed that AID expression is highly specific to, and abundantly expressed in B-cell-derived cancers and that ectopic overexpression of AID leads to rapid cell death. Using a knock-down model, we revealed that AID expression significantly impacts genomic stability, proliferation, migration and drug resistance. Conclusion AID is an important driver of lymphoma, impacting multiple cellular events, and is potentially a strong candidate for targeted therapy in lymphoma.
- Published
- 2021
- Full Text
- View/download PDF