MiR-146a Overexpression in Oral Squamous Cell Carcinoma Potentiates Cancer Cell Migration and Invasion Possibly via Targeting HTT

Liping Wang,Janak L. Pathak,Xueqi Guo,Ying Fang,Linhu Ge,Yunxin Chen,Yucheng Su,Lijing Wang,Yongyong Yan

doi:10.3389/fonc.2020.585976

Abstract

Huntingtin (HTT) is one of the target genes of miR-146-a and regulates various cancer cell activities. This study aims to explore the miR-146a expression pattern in oral squamous cell carcinoma (OSCC) and its role and mechanism in OSCC progression and metastasis via targeting the HTT gene. OSCC tissue and non-cancerous matched tissue (NCMT) were obtained from 14 patients. OSCC cell lines and normal HOK cells were used to analyze migration and invasion assay. OSCC-induced miR-146a knockout mice (B6.Cg-Mir146tm1.1Bal) model was developed. Transwell cell migration/invasion and scratch wound assays were used to investigate the OSCC cell migration and invasion in vitro. Kaplan-Meier survival analysis was used to investigate the association of HTT expression patterns in cancer tissue with patient survival percentage and duration. Pearson’s correlation analysis tested the association between miR-146a and HTT expression in OSCC tissues. miR-146a mimic and inhibitor transfection were performed to overexpress and knockdown the miR-146a in OSCC cells, respectively. miR-146a expression was highly upregulated in OSCC tissues and OSCC cell lines. Cancer cell migration/invasion was enhanced in miR-146a overexpressed cells and reduced in mi-R146a knockdowned cells. HTT expression was reduced in OSCC tissues and cell lines compared to NCMT and HOK cells, respectively. HTT expression was downregulated in miR-146a overexpressed OSCC cells and upregulated in miR-146a knockdowned OSCC cells. The expression pattern of miR-146a in OSCC cell lines and tissues was inversely correlated with HTT expression. Prediction of miRNA target analysis showed that HTT possesses the binding sites for miR-146a. HTT overexpression in OSCC tissues was associated with patients’ higher survival percentage and duration. HTT knockdown in OSCC cells enhanced miR-146a expression and cell migration/invasion. Inducing OSCC in miR-146a knockout mice increased the HTT expression in tongue tissue and alleviated the cancer aggressiveness and epithelial damage. Overexpressed miR-146a in OSCC targets the HTT gene and enhances cancer cell migration/invasion unraveling the possible role of HTT in miR146a-mediated OSCC cell migration and invasion.

Highlights

Oral cavity cancer is the most common head and neck cancer with poor prognosis and a high recurrence rate [1]
Overexpression of miR-146a Promotes Oral squamous cell carcinoma (OSCC) Cell Migration and Invasion miR-146a was transfected in OSCC cells to analyze the effect of miR146a on OSCC cell migration and invasion
This result indicates that the overexpressed miR-146a in OSCC cells promotes cancer cell migration and invasion

Summary

Introduction

Oral cavity cancer is the most common head and neck cancer with poor prognosis and a high recurrence rate [1]. Oral squamous cell carcinoma (OSCC) accounts for more than 90% of all head and neck cancer and is the sixth most common cancer worldwide [2, 3]. Despite the progress of surgery, radiotherapy, and chemotherapy treatments, the 5-year survival rate of OSCC patients was still less than 50% in the last 30 years [2, 4]. OSCC has a high rate of metastasis in the head and neck region due to local invasion and due to lack of early diagnostic markers [5]. The molecular level understanding in OSCC progression and metastasis is necessary to unveil novel diagnostic and therapeutic targets

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