title: Upregulated TRIM29 promotes proliferation and metastasis of nasopharyngeal carcinoma via PTEN/AKT/mTOR signal pathway.
abstract: Tripartite motif-containing 29 (TRIM29) has been reported to be dysregulated in human cancers. Up-regulation of TRIM29 was first observed in NPC cell lines by a genome-wide transcriptome analysis in our previous study. However, its expression biological function and clinical significance in nasopharyngeal carcinoma (NPC) remain unclear. In this study, TRIM29 expression was validated by qRT-PCR and immunohistochemistry in 69 NPC samples. Notably, TRIM29 protein expression was significantly and positively correlated with the tumor size, clinical stage and metastasis. TRIM29 was identified as the direct target of miR-335-5p and miR-15b-5p, both of which were down-regulated and negatively associated with TRIM29 expression in NPC cell lines and clinical samples. Ectopic TRIM29 expression promoted proliferation, epithelial-mesenchymal transition (EMT), migration and invasion in NPC cells, while its depletion inhibited cell invasion and EMT phenotype. Mechanistically, TRIM29 overexpression reduced PTEN expression and increase phosphorylated protein level of AKT, p70S6K and 4E-BP1. Correspondingly, AKT inhibitor and Rapamycin blocked the effect of TRIM29 on cell invasion. In conclusion, our results suggest that miR-335-5p and miR-15b-5p down-regulation results in TRIM29 over-expression, which induces proliferation, EMT and metastasis of NPC through the PTEN/AKT/mTOR signaling pathway.
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Zhou
authors.affiliation: Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors.forename: Dong-Hua
authors.initials: DH
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors.forename: Mei-Yin
authors.initials: MY
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors.forename: Meng-He
authors.initials: MH
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 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
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.|Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors.forename: Shi-Juan
authors.initials: SJ
authors.lastname: Mai
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015996:Survival Rate; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D035683:MicroRNAs; C087296:TRIM29 protein, human; D014157:Transcription Factors; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: TRIM29; metastasis; nasopharyngeal carcinoma; signal pathway