MicroRNA‑655 suppresses cell proliferation and invasion in oral squamous cell carcinoma by directly targeting metadherin and regulating the PTEN/AKT pathway.

Qiang Wang,Honghai Ji,Longkun Lv,Yuan Li

doi:10.3892/mmr.2018.9292

Abstract

MicroRNAs (miRNAs) are important regulators of a variety of biological processes and their dysregulation is closely related to cancer formation and progression. Therefore, examination of aberrantly expressed miRNAs in oral squamous cell carcinoma (OSCC) may provide important clues for the diagnosis and treatment of patients with OSCC. The aim of the present study was to determine miRNA (miR)‑655‑3p expression in OSCC tissues and cell lines, and to investigate the biological roles and mechanisms of miR‑655‑3p associated with OSCC. Data from the present study indicated that miR‑655 expression was significantly downregulated in human OSCC tissues and cell lines. Overexpression of miR‑655 attenuated cell proliferation and invasion in OSCC invitro. Metadherin (MTDH) mRNA was predicted as a potential target of miR‑655 by bioinformatics analysis, and this was confirmed by luciferase reporter assay, reverse transcription‑quantitative polymerase chain reaction and western blot analysis. In OSCC tissues, MTDH was highly expressed and inversely correlated with miR‑655 expression levels. MTDH overexpression reversed the inhibitory effects of miR‑655 mimics in OSCC cells. Notably, the upregulation of miR‑655 expression inhibited the activation of the phosphatase and tensin homolog (PTEN)/RAC‑α serine/threonine‑protein kinase (AKT) pathway in OSCC cells. Therefore, these results may provide the first evidence that miR‑655 targets MTDH to inhibit proliferation and invasion of OSCC by inhibiting PTEN/AKT signaling. Thus, the restoration of miR‑655 expression may be a novel therapeutic strategy for patients with OSCC.

Highlights

Oral cancer is the sixth most common malignant neoplasm worldwide [1]; oral squamous cell carcinoma (OSCC) is the most common type of oral cancer and accounts for ~90% of all oral cancer cases, with an estimated 300,000 new cases diagnosed per year [2]
Tca8113 and CAL‐27 cells, and Reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) was performed to measure the levels of miR‐655 expression. (B) Proliferation was evaluated by MTT assay for cells transfected with miR‐655 mimics or miR‐NC. (C) Effects of miR‐655 on cell invasion were determined by Matrigel cell invasion assay. *P
The data indicated that miR‐665 expression was significantly lower in OSCC cell lines compared with expression in normal human oral keratinocytes (NHOK) cells (Fig. 1B; P

Summary

Introduction

Oral cancer is the sixth most common malignant neoplasm worldwide [1]; oral squamous cell carcinoma (OSCC) is the most common type of oral cancer and accounts for ~90% of all oral cancer cases, with an estimated 300,000 new cases diagnosed per year [2]. Despite remarkable improvements in diagnostic strategies and surgery, the clinical outcome of patients diagnosed with OSCC remains unsatisfactory, with a 5‐year survival rate of

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