miR-144-3p, a tumor suppressive microRNA targeting ETS-1 in laryngeal squamous cell carcinoma

Abstract

// Si-Yi Zhang 1, * , Zhong-Ming Lu 1, * , Ye-Feng Lin 1 , Liang-Si Chen 1 , Xiao-Ning Luo 1 , Xin-Han Song 1 , Shao-Hua Chen 1 , Yi-Long Wu 2 1 Department of Otorhinolaryngology, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong Province, China 2 Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong Province, China * These authors contributed equally to this work Correspondence to: Yi-Long Wu, e-mail: syylwu@live.cn Si-Yi Zhang, e-mail: szhang555@hotmail.com Keywords: biomarker, laryngeal squamous cell carcinoma, migration, miR-144-3p, prognosis Received: June 12, 2015      Accepted: November 28, 2015      Published: January 27, 2016 ABSTRACT Regional lymph node metastasis and distant metastasis are critical in the prognosis of laryngeal squamous cell carcinoma (LSCC). This study investigated the roles of miR-144-3p and E26 transformation specific-1 (ETS-1) in the invasion and migration of LSCC cells. The effects of miR-144-3p and ETS-1 on FaDu and Hep2 cell growth, migration and invasion were determined. Suppression of ETS-1 by miR-144-3p was confirmed using luciferase assays; the effects of ETS-1 silencing were determined using a xenograft tumor model. The expression of ETS-1 was analyzed in 71 paraffin-embedded tissue biopsies and eight fresh frozen biopsies obtained from LSCC patients. miR-144-3p inhibited the growth, invasion and migration of FaDu and Hep2 cells in part through suppression of epithelial-mesenchymal transition as determined by increased E-cadherin and α-catenin and reduced fibronectin and vimentin expression. Additionally, ETS-1 is a molecular target of miR-144-3p, and silencing ETS-1 expression inhibited FaDu and Hep2 cell invasion and migration as well as reduced Hep2 xenograft tumor volume. In LSCC, the expression of ETS-1 is upregulated with disease progression, and higher ETS-1 expression, which was negatively associated with miR-144-3p levels, adversely corresponded with prognoses. Thus, upregulated ETS-1 levels may promote LSCC metastasis, resulting in poor patient prognosis.