MiR-876-5p modulates head and neck squamous cell carcinoma metastasis and invasion by targeting vimentin

Yibo Dong,Yang Zheng,Yifei Du,Yunong Wu,Laikui Liu,Yi Zhong,Xu Ding,Wei Zhang,Xiaomeng Song,Chundi Wang

doi:10.1186/s12935-018-0619-7

Abstract

BackgroundLocal or distant metastasis remains the main course of death in head and neck squamous cell carcinoma (HNSCC) patients. MicroRNAs (miRNAs) have been implicated in metastasis of HNSCC, but the mechanisms of their action are mainly undocumented. Through public head and neck cancer miRNA expression datasets, we found that miR-876-5p was a novel potential tumor suppressor targeting HNSCC metastasis.MethodsClinical significance and mechanism of miR-876-5P was systematically analyzed in HNSCC. Quantitative RT-PCR was used to evaluate miR-876-5p levels in HNSCC cell lines and in 20 pairs of HNSCC with associated regional nodal metastases and HNSCC without metastatic primary tumors. Scratch and invasion assays were evaluated to determine the role of miR-876-5p in the regulation of HNSCC cell migration and invasion, respectively. Western blotting was used to investigate the mechanism by which miR-876-5p suppresses HNSCC cell invasion and migration. Luciferase assays were performed to assess miR-876-5p binding to the vimentin gene. The animal model was used to support the in vitro experimental findings.ResultsMiR-876-5p mimics inhibited HNSCC cell migration and invasion. Vimentin protein and mRNA levels were decreased in the miR-876-5p mimics group but increased in the miR-876-5p inhibitors group, which demonstrated that miR-876-5p inhibits vimentin expression in HNSCC cells. By directly targeting the vimentin 3′-UTR, we used dual-luciferase reporter assays to verify that vimentin is a functional downstream target of miR-876-5p. Importantly, increased vimentin expression promoted cell migration and invasion, and co-transfection with miR-876-5p mimics and vimentin restored cell aggressiveness to the original level. Moreover, miR-876-5p overexpression significantly downregulated vimentin expression level and inhibited the distal metastasis of HNSCC cells in vivo.ConclusionsmiR-876-5p, which functions as a tumor suppressor in HNSCC, inhibits metastasis by targeting vimentin and provides a novel therapeutic target for HNSCC treatment.

Highlights

Local or distant metastasis remains the main course of death in head and neck squamous cell carcinoma (HNSCC) patients
Vimentin protein and mRNA levels were decreased in the miR-876-5p mimics group but increased in the miR-876-5p inhibitors group, which demonstrated that miR-876-5p inhibits vimentin expression in HNSCC cells
Tissues with lymph node metastasis (Table 1), our results revealed that miR-876-5p expression was significantly lower in HNSCC tissues with lymph node metastasis than that in HNSCC without metastatic primary tumors (Fig. 1a)

Summary

Introduction

Local or distant metastasis remains the main course of death in head and neck squamous cell carcinoma (HNSCC) patients. Through public head and neck cancer miRNA expression datasets, we found that miR-876-5p was a novel potential tumor suppressor targeting HNSCC metastasis. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world [1]. More than half of the newly diagnosed HNSCC patients have been reported to suffer from advanced-stage disease, and the majority of them may cause the spread of the tumor into the cervical regional draining lymph nodes [2]. It has been reported that downregulation of let-7a was associated with the presence of perineural invasion and upregulation of miR-145 and miR-205 in HNSCC samples was associated with the existence of vascular invasion and lymph node metastasis, respectively [9]. There are still few investigations related to tumor suppressor microRNAs associated with lymph node metastases

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Discussion

Conclusion