title: 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.
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Xu
authors.affiliation: Department of Basic Medicine, Guiyang College of Traditional Chinese Medicine, Guiyang, China.
authors.forename: Jingye
authors.initials: J
authors.lastname: Hu
authors.affiliation: Gynecology and Obstetrics Department, Women and Children's Medical Center, Guangzhou, China.
authors.forename: Tiansong
authors.initials: T
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors.forename: Hui-Yun
authors.initials: HY
authors.lastname: Wang
mesh_terms: D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011379:Prognosis; D034622:RNA Interference; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D060449:Wnt Signaling Pathway / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics*
chemical_list: D015820:Cadherins; D004268:DNA-Binding Proteins; C087296:TRIM29 protein, human; D014157:Transcription Factors; D051176:beta Catenin
keywords: TRIM29; cervical cancer; metastasis; prognosis; proliferation