MicroRNA-493 suppresses tumor growth, invasion and metastasis of lung cancer by regulating E2F1.

Yixue Gu,Chengkun Wang,Ye Cheng,Zhimin He,Zhijie Zhang,Ying Song,Min Deng,Guopei Zheng

doi:10.1371/journal.pone.0102602

Abstract

miRNAs have been proposed to be key regulators of progression and metastasis in cancer. However, an understanding of their roles and molecular mechanisms is needed to provide deeper insights for better therapeutic opportunities. In this study we investigated the role and mechanism of miR-493 in the development and progression of nonsmall-cell lung cancer (NSCLC). Our data indicated that the expression of miR-493 was markedly reduced in pulmonary carcinoma. The ectopic expression of miR-493 impaired cell growth and invasion in vitro and in vivo. Mechanically, miR-493 commonly directly targeted E2F1, which resulted in a robust reduction of the expression of mRNA and protein. This effect, in turn, decreased the growth, invasion and metastasis of lung cancer cells. Our findings highlight the importance of miR-493 dysfunction in promoting tumor progression, and implicate miR-493 as a potential therapeutic target in lung cancer.

Highlights

Lung cancer is the most prevalent histological cancer subtype worldwide [1]
We identified that miR-493, a potentially candidate tumor suppressor miRNA [22,23], was markedly reduced in lung cancer and that lower miR-493 expression was associated with tumor metastasis and poor prognosis
The overexpression of E2F1 is frequently associated with high-grade tumors and poor patient survival prognosis [29,31,34], suggesting that its oncogenic properties extend beyond the ability to stimulate the aberrant growth of neoplastic cells

Summary

Introduction

Because the majority of patients present with invasive, metastatic disease [2], understanding the basis of lung cancer progression is vital. Many factors, including tumor suppressors and oncogenes, are involved in pulmonary tumorigenesis or progression. The classical members of protein-encoding genes have been expanded to include a type of non-protein-coding RNA molecule known as microRNA (miRNA) [5,6,7]. MiR-34 reportedly prevents cancer initiation and progression in lung adenocarcinoma [13]. MiRNA-218, a new regulator of HMGB1, reportedly suppresses cell migration and invasion in non-small cell lung cancer [14]. Further knowledge of the molecular mechanisms of miRNA is needed to provide deeper insights to develop better therapeutic opportunities for patients with lung cancer

Methods

Results

Conclusion