MiR-138 suppresses the proliferation of oral squamous cell carcinoma cells by targeting Yes-associated protein 1.

Ran Xu,Qingna Zhang,Zhe Zhang,Jinxiu Zhao,Yue Ren,Daxu Li,Jing Gao,Guang Zeng,Hong Tao

doi:10.3892/or.2015.4144

Abstract

Aberrant microRNA expression has been suggested to be an important event in the pathologies of various types of cancer. MicroRNA-138 (miR-138) has been reported to be frequently downregulated in various types of human cancer, including oral squamous cell carcinoma (OSCC). However, the precise molecular mechanism of miR-138 underlying OSCC remains largely unknown. The aim of the present study was to investigate the expression of miR-138 in OSCC tumor tissues and several OSCC cell lines and validated its interaction with the 3'-untranslated region (3'-UTR) of Yes-associated protein 1 (YAP1). The results showed that, miR-138 was significantly downregulated in OSCC tumor tissues and cell lines. Overexpression of miR-138 inhibited cell proliferation of OSCC cells whereas the downregulation of miR-138 promoted cell proliferation. A direct interaction between miR-138 and 3'-UTR of YAP1 was validated by dual-luciferase reporter assay. Moreover, overexpression of miR-138 in OSCC cells significantly decreased the expression of YAP1 and downregulation of miR-138 inhibited the expression of YAP1. Specifically, the inhibitory effect of miR-138 on the proliferation of OSCC cells was eliminated by transfection with YAP1 overexpression vectors that did not harbor any specific miR-138 binding specific sequences in 3'-UTR. In addition, the miR-138‑overexpressing OSCC cells exhibited a low growth rate in the xenograft tumor assay with a decreased expression of YAP1 in tumor tissues. The results suggest that miR-138 is a tumor suppressor miRNA in OSCC through targeting YAP1, which serves as a promising therapeutic target for the treatment of OSCC.

Highlights

Oral squamous cell carcinoma (OSCC) is one of the life‐threatening cancer types worldwide with a high frequency of recurrence and a low survival rate [1,2]
We have reported that a decreased expression of miR-138 in OSCC tumor tissues and OSCC
To the best of our knowledge, for the first time, we have delineated a direct interaction of miR-138 and Yes-associated protein 1 (YAP1) that may be involved in the regulation of OSCC

Summary

Introduction

Oral squamous cell carcinoma (OSCC) is one of the life‐threatening cancer types worldwide with a high frequency of recurrence and a low survival rate [1,2]. MiRNAs are capable of targeting the 3'-untranslated region (3'-UTR) of messenger RNA (mRNA) containing the corresponding complementary sequences that results in mRNA destabilization and degradation, thereby leading to protein translational inhibition [6]. Given their ability to modulate gene expression, miRNAs have been found to participate in many cell processes, including cell growth and proliferation, differentiation, apoptosis; miRNAs are involved in the pathologies of various diseases [7,8]. Downregulation of miR-329 and miR-410 increased the proliferation and invasion of OSCC cells by targeting and regulating the expression of Wnt-7b [12].

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