Abstract 177: Role and mechanisms of miR-223 in the invasion and metastasis of head and neck squamous cell carcinoma

Abstract

Abstract Purpose: Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies with a low survival rate for its ability of metastasis. Therefore, finding the potential biomarkers for the diagnostic, as well as therapy and prognostic of HNSCC metastasis is extremely urgent. Previous studies have demonstrated that microRNAs, a 21-23 nucleotide strands of endogenous single-stranded RNAs, which could regulate the expression of numerous genes post-transcriptionally, played a key role in the invasion and metastasis of human cancer. In this study, we attempted to explore the function and mechanism of microRNAs in invasion and migration of HNSCC, and hoped to provide a novel diagnostic and therapeutic strategy for HNSCC patient with metastasis. Materials and Methods: In order to identify a new microRNA/gene pathway that regulates the invasion and metastasis in HNSCC, we performed a microarray assay to explore the microRNAs expression profiling in HNSCC cells with varying invasiveness. Quantitative RT (qRT)-PCR and functional analysis were used to confirm the role of microRNA, which we focused on, in HNSCC invasion. Then we predicted the targeted gene of microRNA through a bioinformatics approach and defined it by luciferase assay and western blot. At last, we utilized the buccal mucosa-lymph node metastasis model to detect the effect of microRNA in HNSCC metastasis in vivo. Results: Here, we established the role and mechanisms of miR-223 in metastasis of HNSCC. First, we profiled microRNA expression in four HNSCC cells with varying invasive capacity. MiR-223 was highly down regulated in cells with highly invasive capacity. The negative correlation between miR-223 expression and invasiveness was confirmed in another validation cohort of seven HNSCC cells. Functional analysis showed that ectopic expression of miR-223 repressed HNSCC cell invasiveness; on the other hand, miR-223 inhibition resulted in increased HNSCC cell invasiveness. Furthermore, the expression level of TCF7L2, an important transcription factor in Wnt pathway, was repressed when overexpressing the miR-223 expression in HNSCC cells, whereas miR-223 silencing increased its expression. Next, we showed that miR-223 could bind to the 3′-untranslated region of TCF7L2 by luciferase assay. Moreover, we demonstrated that TCF7L2 enhanced the invasion of HNSCC cells, and the silencing of TCF7L2 inhibited invasion. Most importantly, increased miR-223 expression level in HNSCC cell repressed the metastasis of lymph node in vivo, and decreased the miR-223 expression enhanced the metastasis. Conclusions: Taken together, these data indicated that miR-223 played a key role in HNSCC invasion and metastasis by targeting to the 3′UTR of TCF7L2. And our results presented evidences for a potential anti-metastasis therapeutic value of miR-223 in HNSCC patients. Citation Format: Yun Wang, Zhi Wang, Bin Cheng. Role and mechanisms of miR-223 in the invasion and metastasis of head and neck squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 177. doi:10.1158/1538-7445.AM2015-177