Oncotarget

Research Papers:

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

Rui Xu _, Jingye Hu, Tiansong Zhang, Chao Jiang and Hui-Yun Wang

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Oncotarget. 2016; 7:28579-28591. https://doi.org/10.18632/oncotarget.8686

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Abstract

Rui Xu1,2*, Jingye Hu3*, Tiansong Zhang4, Chao Jiang1,2, Hui-Yun Wang1,2

1State Key Laboratory of Oncology in South China, Guangzhou, China

2Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China

3Department of Basic Medicine, Guiyang College of Traditional Chinese Medicine, Guiyang, China

4Gynecology and Obstetrics Department, Women and Children’s Medical Center, Guangzhou, China

*These authors contributed equally to this work

Correspondence to:

Hui-Yun Wang, email: [email protected]

Keywords: TRIM29, prognosis, proliferation, metastasis, cervical cancer

Received: December 21, 2015    Accepted: March 28, 2016    Published: April 12, 2016

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.


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