TRIM65 is a potential oncogenic protein via ERK1/2 on Jurkat and Raji cells: A therapeutic target in human lymphoma malignancies.

In human lung cancer, Tripartite motif 65 (TRIM65) is documented as an important regulator in carcinogenesis. Knockdown of TRIM65 prevents the tumorigenesis of lung cancer cells, while TRIM65 overexpression presents the opposite effect. However, the roles of TRIM65 in human lymphocyte malignancies have reported little. Herein, we found that Jurkat (T-lymphocyte) and Raji (B-lymphocyte) expressed TRIM65. We aimed to investigate whether TRIM65 was a potential oncogenic protein that regulated the tumorigenesis of Jurkat and Raji cells. In our present study, cells were transfected with siRNA-TRIM65 or TRIM65 overexpression vector, Cell counting kit-8 (CCK-8), Flow cytometry and Annexin V-FITC/propidium iodide (PI) staining was carried out to detect cell viability, cell cycle profile and cell apoptosis, respectively. Extracellular signal-regulated kinases 1/2 (ERK1/2) pathway-associated proteins, such as Bcl2, cleaved-caspase 3, vascular endothelial growth factor (VEGF), and phosphorylated ERK1/2 (p-ERK1/2) were assessed. Our data indicated that knockdown of TRIM65 prevented the tumorigenesis of Jurkat and Raji cells. TRIM65 silencing inhibited cell proliferation, promoted cell apoptosis and arrested cell cycle, highly like through blocking ERK1/2 pathway. However, TRIM65 overexpression enhanced cell viability, increased the protein levels of Bcl2, VEGF, p-ERK1/2 while decreased cleaved-caspase 3 expression, suggesting the promoted effect of TRIM65 overexpression in the tumorigenesis of those two lymphoma cells. To validate the involvement of ERK1/2 pathway, ERK1/2 inhibitor AZD8330 (1 µmol/L) was introduced. We found that AZD8330 significantly prevented TRIM65 overexpression-induced tumorigenesis. We concluded that TRIM65 served as a potential oncogenic protein on Jurkat and Raji cells, and ERK1/2 pathway was the underlying mechanism. Approaches targeting TRIM65 provided a novel strategy for the treatment of lymphoma.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}