TRIM28 as an independent prognostic marker plays critical roles in glioma progression

Abstract

Tripartite motif (TRIM) proteins are involved in tumorigenesis. Here, we examined the expression, biological function, and clinical significance of tripartite motif containing 28 (TRIM28) in glioma, a locally aggressive brain tumor. First, TRIM28 expression was significantly higher in glioma (n = 138) than in non-glioma controls (n = 6). TRIM28 expression was positively correlated with tumor malignancy, and associated with poor overall survival (OS) and progression-free survival (PFS). Notably, TRIM28 expression was negatively correlated with p21 expression in patients with glioblastoma multiforme (GBM). A multivariate analysis that included relevant measures indicated that high TRIM28 expression is an independent prognostic factor for poor OS and PFS in GBM patients. In experiments with cultured glioma cells, down-regulating TRIM28 with shRNA increased p21 expression, and induced cell cycle arrest at the G1 phase. In a xenograft model, down-regulating TRIM28 suppressed tumor growth. These results indicate that over-expression of TRIM28 is associated with poor outcome in glioma patients.

miR-491 regulates glioma cells proliferation by targeting TRIM28 in vitro

“…Further study of the physiological and molecular mechanisms of formation and progression of glioma is necessary to development more effective diagnostic and therapeutic approaches. Our previous study demonstrated that knockdown of TRIM28 in glioma cells suppressed cell proliferation, which could be partially explained by the negative correlation between TRIM28 and p21 expression in GBM patients [5]. Our present study indicated an aberrant expression of miR-491 in GBM specimens and that TRIM28 protein levels negatively correlates with miR-491 expression from TCGA database and our cohort.…”

“…TRIM28, a member of TRIM family, expression of which has been verified to be up-regulated in several tumors; for instance, lung cancer, breast cancer and gastric cancer [3, 4]. We demonstrated a positive correlation between TRIM28 expression and glioma malignancy in a previous study [5]. Both in vitro and in vivo, higher expression of TRIM28 lead to a worse prognosis via promotion of the proliferation ability of glioma cells.…”

“…Colony formation assay and proliferation assay were carried out as previously introduced [5]. We repeated every experiment at least three times.…”

“…We performed total RNA isolation, cDNA synthesis and qRT-PCR as previously introduced [5]. GAPDH was used as an internal standard.…”

“…Western blotting was carried out as previously introduced [5]. Rabbit anti-human TRIM28 (ab10483, Rabbit, 1:1000; Abcam, Cambridge, MA, USA) was selected to examine TRIM28 expression.…”