Abstract
Tongue squamous cells carcinoma (TSCC) is one of the most lethal malignancies of oral cancers and its prognosis remains dismal due to the paucity of effective therapeutic targets. Herein, we showed that Tripartite motif containing 14(TRIM14) is markedly up-regulated in TSCC cell lines and clinical tissues. Immunohistochemical (IHC) analysis of 116 clinical TSCC specimens revealed that TRIM14 expression was significantly correlated with the TNM classification (T: P = 0.01; N: P < 0.001; M: P < 0.001) in patients with TSCC. Multivariate analysis indicated that TRIM14 expression might be an independent prognostic indicator for the survival of patients with TSCC. Ectopic expression of TRIM14 in TSCC cells promoted proliferation, angiogenesis, and increased resistance to cisplatin-induced apoptosis of TSCC cells in vitro. Furthermore, TRIM14 overexpressing significantly promoted the tumorigenicity of TSCC cells in vivo whereas silencing endogenous TRIM14 caused an opposite outcome. Moreover, we demonstrated that TRIM14 enhanced TSCC aggressiveness by activating NF-κB signaling. Together, our results provide new evidence that TRIM14 overexpression promotes the progression of TSCC and might represent a novel therapeutic target for its treatment.
Highlights
Oral squamous cell carcinoma (OSCC) represents the sixth most common solid cancer worldwild and tongue squamous carcinoma (TSCC) is one of the major oral malignant tumor subtypes [1,2,3]
By analyzing the published mRNA expression profiles obtained from 31 TSCC tissues and 27 normal tongue tissues (NCBI/GEO/GSE13601), we found that Tripartite motif containing 14 (TRIM14) was significantly upregulated in TSCC tissues compared with normal tissues (Figure 1A)
Real-time PCR and western blotting analyses revealed that TRIM14 was markedly overexpressed in all five TSCC cell lines and HIOEC immortalized oral epithelial cells, at both the protein and mRNA levels, compared with two normal tongue epithelial cells normal tongue epithelial cell lines (NTECs) (Figure 1B and Supplementary Figure 1A)
Summary
Oral squamous cell carcinoma (OSCC) represents the sixth most common solid cancer worldwild and tongue squamous carcinoma (TSCC) is one of the major oral malignant tumor subtypes [1,2,3]. The clinical treatment outcomes for tongue cancer have improved in recent decades, the overall 5-year survival rate for TSCC patients is only 50% due to lacking of new diagnostic and treatment methods [5, 6]. It is of great clinical value to explore the molecular mechanisms in development of TSCC and identify effective treatment strategies to improve the survival rate for TSCC patients. Accumulating evidences suggest that poor therapeutic effect and the dismal survival rate of TSCC are associated with aberrantly activated signaling pathways, including nuclear factor-κB (NF-κB) signaling [7]. Blockade of NF-κB signaling contributed the antitumor activity of Trichostatin A in human tongue carcinoma cells [9] and the down-regulation of NF-κB p65 can inhibit invasion and migration of human tongue www.impactjournals.com/oncotarget cancer SCC4 cells induced by gypenosides [10]. Discovering novel molecular(s) that can regulate aberrant activation of the NF-κB pathway could be important for clinical TSCC therapy
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