circRNA: circular RNA; miRNA: microRNA; RNA-FISH: RNA fluorescence in situy bridization; qRT-PCR: Reverse transcription and quantitative real-time PCR.

Circular RNAs (circRNAs) are reported to regulate the development and progression of multiple cancers. However, the functions of circRNAs in nasopharyngeal carcinoma (NPC) are unclear. In this study, we identified that circular homeodomain interacting protein kinase 3 (circHIPK3) was highly expressed in NPC tissues and cell lines. Moreover, we found that circHIPK3 expression levels could act as a prognostic marker in NPC patients. We showed that circHIPK3 silence repressed NPC cell proliferation, migration, and invasion in vitro. In addition, circHIPK3 depletion dramatically repressed tumor growth and metastasis in vivo. Mechanistically, we revealed circHIPK3 as a competing endogenous RNA of microRNA (miR)-4288 that targets E74-like ETS transcription factor 3 (ELF3) in NPC cells. We found that miR-4288 inhibition reversed the effects of circHIPK3 silence on NPC cells. Furthermore, rescue assays also indicated that circHIPK3 promoted the malignant behaviors of NPC cells via enhancing ELF3 expression by suppressing the miR-4288 levels. In conclusion, our findings demonstrated that circHIPK3 facilitated NPC progression through protecting ELF3 from miR-4288-mediated silencing, which suggested that the circHIPK3-miR-4288-ELF3 regulatory loop might be a potential target for NPC prevention.

Steroid receptor coactivator 1 (Src-1) and Twist1 are aberrantly upregulated in a variety of tumors and play an important role in tumor progression. However, the exact role of Src-1 and Twist1 in nasopharyngeal carcinoma (NPC) is uncertain. In this study, we investigated the possible prognostic value and biological effect of Src-1 and Twist1 in NPC. Src-1 and Twist1 expression was detected in a cohort of NPC patients (n = 134) by qRT-PCR. Kaplan-Meier survival analysis was used comparing overall survival (OS) and progression-free survival (PFS). Multivariate analysis was performed using the Cox proportional hazard regression model. Biologic effect of Src-1 and Twist1 in NPC cell lines was evaluated by western blot, colony formation assay, soft agar assay, scratch wound healing assay, transwell invasion assay and tumor xenografts growth. We have found that Src-1 and Twist1 were aberrantly upregulated in human NPC tissues, and associated with advanced tumor stage, distant metastasis and unfavorable prognosis. Knockdown of Src-1 or Twist1 in human NPC cell line CNE-1 suppressed colony formation, anchorage-independent growth, cell migration, invasion and tumor xenografts growth, while enforced expression of Src-1 or Twist1 in human NPC cell line HNE-2 promotes anchorage-independent growth, cell migration and invasion. In addition, Src-1 and Twist1 could suppress E-cadherin expression and increase Vimentin expression, thus suggested that Src-1 and Twist1 enhanced the malignant behaviors of NPC cells via inducing epithelial-mesenchymal transition (EMT). Our data indicated that Src-1 and Twist1 could be possible prognostic biomarkers and potential therapy targets for patients with NPC.

Laryngeal squamous cell carcinoma (LSCC) is the main pathological type of laryngeal cancer, which attacks the head and neck.