TRIM29 overexpression is associated with poor prognosis and promotes tumor progression by activating Wnt/β-catenin pathway in cervical cancer

Abstract

Dysregulation of TRIM29 has been reported to be involved in tumorigenesis, but the role of TRIM29 in cervical cancer is unclear. In this study, we first examined TRIM29 expression and found that TRIM29 mRNA and protein expression was upregulated in cervical cancer tissues when compared with the matched adjacent cervical tissues. We further detected TRIM29 protein with immunohistochemistry in 150 paraffin-embedded samples from early-stage cervical cancer patients. The results showed that high expression of TRIM29 was significantly associated with pelvic lymph node metastasis (p=0.002), advanced FIGO stage (p=0.026) and post-operative recurrence (p<0.001). Patients with high expression of TRIM29 had a shorter overall survival (HR 5.042, p<0.001) and disease-free survival (HR 4.260, p<0.001). TRIM29 was proven to be an independent prognostic factor for cervical cancer patients. When endogenous TRIM29 expression was knocked down by siRNAs, cell proliferation, colony formation, migration and invasion in cervical cancer cell lines HeLa and SiHa were obviously inhibited. Meanwhile, TRIM29 knockdown increased E-cadherin expression but decreased the expression of N-cadherin and β-Catenin, which indicated that TRIM29 could promote epithelial-mesenchymal transition (EMT). Mechanically, knockdown of TRIM29 enhanced GSK-3β protein expression and inhibited the expression of β-Catenin and C-myc proteins. GSK-3β is a key upstream suppressor of β-Catenin and c-myc expression is an indicator of Wnt/β-Catenin activity. Therefore, these results demonstrate that TRIM29 promotes tumor progression by activating Wnt/β-Catenin signaling. In conclusion, TRIM29 is overexpressed and associated with survival of early-stage cervical cancer, indicating that TRIM29 may be a potential prognostic biomarker and therapeutic target for cervical cancer.

ATDC promotes the growth and invasion of hepatocellular carcinoma cells by modulating GSK‐3β/Wnt/β‐catenin signalling

“…of Wnt/β-catenin signalling during tumour progression has been highlighted in recent years. Multiple sources of evidence have demonstrated that ATDC promoted the activation of Wnt/β-catenin signalling in various cancers, including non-small-cell lung cancer, cervical cancer, colorectal cancer, pancreatic cancer and glioma 25,29,[47][48][49]. Consistent with these findings, our results demonstrate that ATDC contributes to the activation of Wnt/β-catenin signalling in HCC cells.…”

“…13,14,26 ATDC is reported to promote the growth and metastasis of various tumours in vitro or in vivo. 15,16,25,[27][28][29][30][31][32][33] A recent study reports that ATDC is essential for TP63-regulated basal cancer invasive program. 34 Moreover, ATDC exerts its oncogenic effect by promoting the radioresistance and chemo-resistance of tumour cells.…”

TRIM29 promotes progression of thyroid carcinoma via activating P13K/AKT signaling pathway

“…Wang et al also indicated that TRIM29 played a crucial role in DNA damage signaling and radioresistance in human pancreatic cancer cells (21). Xu et al demonstrated that TRIM29 was a novel prognostic biomarker for prediction in aggressive cervical cancer patients that need postoperative adjuvant chemoradiotherapy (22). Liu et al suggested that silencing of TRIM29 enhanced chemosensitivity to cisplatin in human lung squamous cancer by increasing cell apoptosis (10).…”

High expression of TRIM29 (ATDC) contributes to poor prognosis and tumor metastasis by inducing epithelial-mesenchymal transition in osteosarcoma

“…In mouse and human PanIN lesions, TRIM29 was found to upregulate CD44 via activation of β-catenin signaling, which leads to induction of the EMT phenotype characterized by expression of ZEB1 and Snail (47). In cervical cancer cells, knockdown of TRIM29 was shown to increase E-cadherin expression but decrease N-cadherin and β-catenin expression, which also indicates that TRIM29 promotes EMT (48).…”