Knockdown of Tripartite Motif Containing 28 suppresses the migration, invasion and epithelial-mesenchymal transition in ovarian carcinoma cells through down-regulation of Wnt/β-catenin signaling pathway.

Abstract

Tripartite motif containing 28 (TRIM28) is a transcriptional corepressor of Kruppel-associated box zinc finger protein, which has been reported to participate in carcinogenesis. Nonetheless, whether TRIM28 plays a role in the metastasis of ovarian carcinoma (OC) is unclear and requires further investigation. In this study, two OC cell lines (A2780 and OVCAR-3) with stable low expression of TRIM28 were established via RNA interference. We found that the migratory and invasive ability of TRIM28-silenced OC cells significantly decreased. The expression and activity of matrix metallopeptidase (MMP)-2 and MMP-9 in these OC cells were inhibited. The TRIM28 shRNA also suppressed the epithelial-mesenchymal transition (EMT) of OC cells as evidenced by the up-regulated E-cadherin and the downregulated Vimentin and N-cadherin. Additionally, the Wnt/β-catenin signaling pathway was suppressed in TRIM28-silenced OC cells: the activity of β-catenin was inhibited, the expression of total and nuclear β-catenin, Axin 2, T-cell factor 1 (TCF1) and lymphoid enhancer binding factor 1 (LEF1) were decreased, whereas the phosphorylation of β-catenin at Ser33/37 was enhanced. Further, re-expression of active β-catenin in TRIM28-silenced OC cells partly restored their metastasis in vitro. Taken together, our study demonstrates a contributory role of TRIM28 in OC metastasis in vitro, suggesting TRIM28 as a novel therapeutic target for this malignant tumor.