TRIM21 overexpression promotes tumor progression by regulating cell proliferation, cell migration and cell senescence in human glioma.

ABSTRACT

Molecular biomarkers combined with histopathological examination are of critical importance in the diagnosis and treatment of gliomas. Although recent studies have shown that many tripartite motif-containing (TRIM) family proteins could regulate the cell cycle, cell proliferation, and differentiation in cancers, the precise role of TRIM21 has been unknown in glioma. In this study, we analyzed TRIM21, which was upregulated in gliomas and identified its role in tumor proliferation, migration and drug resistance. By using immunohistochemical analysis, we found that the expression level of TRIM21 was upregulated in glioma specimens and the higher expression level of TRIM21 was associated with poorer clinical outcomes in glioma patients. Moreover, we demonstrated that TRIM21 could act as a regulator of the proliferation, cell cycle, and migration of glioma cells by gain- and loss-of function assays in vitro. In vivo, TRIM21 could also modulate glioma progression in murine intracranial xenografts. Furthermore, we found that TRIM21 suppressed cellular senescence via the p53-p21 pathway, and increased drug resistance in glioma cells by RNA-seq analysis, SA-ß-Gal activity assay, and Cell Counting Kit-8 (CCK-8) assay. These results indicated that TRIM21 is a novel regulator in the diagnosis, prognosis, and therapy of gliomas.