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

Abstract

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.

LncRNA LINC01857 promotes growth, migration, and invasion of glioma by modulating miR‐1281/TRIM65 axis

“…For instance, Wei et al reported that TRIM65 increases progression of bladder urothelial carcinoma through upregulating ANXA2 degradation (Wei et al, ). J. Wang et al () indicated that TRIM65 is an oncogene in human lymphoma malignancies. Yang, Zhang, Tian, and Zhang, () showed that TRIM65 contributed to hepatocellular carcinoma development by enhancing β‐catenin pathway.…”

“…J. Wang et al (2018) indicated that TRIM65 is an oncogene in human lymphoma malignancies. Yang, Zhang, Tian, and Zhang, (2017) showed that TRIM65 contributed to hepatocellular carcinoma development by enhancing β-catenin pathway.…”

Autophagy Regulation by Crosstalk between miRNAs and Ubiquitination System

“…TRIM proteins are involved in the regulation of carcinogenesis, autophagy and chemoresistance [ 93 ], for instance, TRIM32 in breast cancer [ 94 ], and TRIM14 in gliomas [ 95 ]. TRIM65 is often overexpressed in cancer tissues and is considered to be an oncogenic protein [ 96 , 97 , 98 , 99 ]. It has been reported that TRIM65 is an E3 ubiquitin ligase for trinucleotide repeat containing six (TNRC6) proteins, which is a component of RNA-induced silencing complex (RISC), and participates in miRNA-induced gene silencing [ 100 ].…”

The Emerging Roles of Tripartite Motif Proteins (TRIMs) in Acute Lung Injury

“…Further studies showed that monocytes/macrophages were higher in the BAL from TRIM65 −/− mice, by which TRIM65 selectively targets vascular cell adhesion molecule 1 (VCAM-1) and directly induces its ubiquitination degradation in endothelial cells. It is worth noting that TRIM65 does not affect the MAPK and NF- κ B signaling pathways in ALI, although some studies have revealed that TRIM65 can activate the Erk1/2 pathway [ 95 , 96 ], which suggests that TRIM65 has diverse functions in different cells and under distinct pathological conditions. Furthermore, TRIM65 is enriched in endothelial cells and declined at the early stage during endothelial activation; the mechanisms that precisely regulate TRIM65 levels in endothelial inflammation remain unknown.…”