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.

TRIM32 promotes cell proliferation and invasion by activating β‐catenin signalling in gastric cancer

“…Xue et al24 showed that TRIM33 as a tumour suppressor that can abrogate tumour cell proliferation and tumorigenesis by degrading nuclear β‐catenin. Knockdown of TRIM28 or TRIM44 suppresses the tumorigenesis by down‐regulating the Wnt/β‐catenin signalling pathway 25, 26. β‐Catenin can also be triggered by TRIM65 via enhancement of the ubiquitination of Axin1 in the progression of hepatocellular carcinoma 27.…”

“…Knockdown of TRIM28 or TRIM44 suppresses the tumorigenesis by down-regulating the Wnt/β-catenin signalling pathway. 25,26 β-Catenin can also be triggered by TRIM65 via enhancement of the ubiquitination of Axin1 in the progression of hepatocellular carcinoma. 27 In the present study, we found that β-catenin was down-regulated by TRIM32 knockdown in SGC7901 and AGS cells and was up-regulated in MKN28 cells with TRIM32 overexpression.…”

MicroRNA‑100 functions as a tumor suppressor in cervical cancer via downregulating the SATB1 expression and regulating AKT/mTOR signaling pathway and epithelial‑to‑mesenchymal transition

“…Epithelial-to-mesenchymal transition (EMT) is a notable process involved in tumor-associated metastases and invasion (8). In the progress of EMT, obvious changes on cell adhesion, polarities, and motile property have been confirmed.…”

Negative Regulation of BOK Expression by Recruitment of TRIM28 to Regulatory Elements in Its 3′ Untranslated Region

“…Along that line, a molecular process potentially linking TRIM28 and BOK could be EMT. Knockdown of TRIM28 was shown to impair EMT in ovarian cancer cells by upregulation of E-cadherin (CHD1) and reduction of vimentin ( VIM ) and N-cadherin (CDH2) ( Deng et al., 2017 ). Along the same line, Chen and colleagues reported that, in NSCLCs, TGFβ-induced EMT is dependent on induction of TRIM28, strongly suggesting that TRIM28 contributes to EMT in NSCLC ( Chen et al., 2014 ).…”