Objectives: 

TRIM59 belongs to the TRIM family of proteins, although little is known about its function, recent studies have suggested that TRIM59 could regulate cell proliferation. Our previous results have shown that TRIM59 expression is increased in tumor samples from mouse models of cancer. Here we address the hypothesis that TRIM59 could act as an oncogene in humans.

Materials: 

RT-qPCR was used to determine TRIM59 expression in human tumor samples. To study proliferation, cell cycle profiles and checkpoint activation were assessed upon Trim59-YFP overexpression in different cell lines, YFP-positive cells were followed by flow cytometry. Silencing was achieved by infect lung adenocarcinoma A549 cells with lentivirus carrying a small hairpin RNA against TRIM59. The established cell line with lower levels of Trim59 was used to study the effects of treatment with cisplatin and to address epithelial-to-mesenchymal transition (EMT) by TGFβ in absence of TRIM59.

Results: 

To explore the oncogenic function of TRIM59, we first study its expression in different human tumor types. In agreement with the results in animal models, we found higher levels of TRIM59 mRNA in non-small cell lung carcinomas, colon tumors and gliomas. Moreover, the survival rate of patients with glioma is low when TRIM59 levels are high. To study the effects of differential TRIM59 expression in human cell lines we did transient overexpression studies, as well as gene silencing in cell cultures. In different cell lines, ectopic expression of TRIM59 caused alteration in cell cycle profile, with S/G2-M accumulation, as well as activation of markers of the DNA damage response, a finding consistent with oncogenic stress induced upon activation of well-characterized oncogenes. Finally, TRIM59 silencing in the A549 cell line caused an impaired response to cisplatin treatment, as well as defects in the EMT induced by TGFβ.

Conclusions: 

In summary our results suggest that TRIM59 acts as an oncogene in human cells and that its function could be related to DNA damage response and EMT induction.