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.
Highlights
Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia, with a high incidence rate of approximately 10-50/100,000 per year [1, 2]
With RNA sequencing, Tripartite motif–containing 29 (TRIM29) mRNA was found to be highly overexpressed in nasopharyngeal carcinoma (NPC) cell lines C666-1 and CNE2 compared with non-NPC NP69 cells, which was confirmed by quantitative real-time PCR (qRT-PCR)
TRIM29 protein is undetectable in non-neoplastic cell line NP69, whereas it can be detected in different expression level in all of NPC cell lines (Figure 1B)
Summary
Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia, with a high incidence rate of approximately 10-50/100,000 per year [1, 2]. NPC is generally sensitive to radiation therapy and the 5-year survival rate of stage I and II NPC treated with radiotherapy is up to 90% [3]. Despite substantial improvements in radiation technique and concurrent-adjuvant chemotherapy during the recent decades, the prognosis for advanced NPC III and IV) is still poor with a 5-year survival rate range from 50% to 70% [5, 6]. Metastasis is the main obstacle in the current clinical management of NPC. A clearer understanding of the molecular bases of NPC metastasis is critical for further improving the survival rate of patients with NPC
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