MicroRNA-1 suppresses proliferation, migration and invasion by targeting Notch2 in esophageal squamous cell carcinoma

Wenzhi Liu,Hailong Shi,Shan Zhu,Mengkao Li,Cheng Cheng,Baosheng Li,Dawei Zhang,Xiangming Chen

doi:10.1038/s41598-018-23421-3

Abstract

MicroRNAs play an important role in the migration and invasion of tumors, and lower expression of microRNA-1 (miR-1) has been proven in a variety of malignant tumors, including esophageal squamous cell carcinoma (ESCC). In this study, we found that miR-1 expression levels in tumor tissues and preoperative serum from esophageal carcinoma patients were lower than those in non-tumorous tissues and healthy volunteers. miR-1 expression in tissues and plasma was closely related to invasion, lymph node metastasis and TNM staging. Additionally, miR-1 expression levels in tissues and plasma were positively correlated. miR-1 inhibited cell proliferation, migration and invasion. Overexpression of miR-1 in ESCC cells reduced Notch2 protein but not mRNA levels, whereas suppression of miR-1 led to an increase in Notch2 protein but not mRNA levels. A dual-luciferase experiment validated that Notch2 was a direct target of miR-1. Introducing Notch2 mRNA into cells over-expressing miR-1 partially abrogated the effects of miR-1 on migration and invasion. Further studies verified that miR-1 regulates EMT signalling pathways directly through Notch2. Therefore, these results confirm that, as a tumor suppressor gene, miR-1 may be a potential tumor marker for the early diagnosis of ESCC and a new drug target.

Highlights

Esophageal cancer is the world’s eighth most malignant tumor and has a 5-year-survival rate of less than 15%1
Expression of miR-1 in 69 esophageal squamous cell carcinoma (ESCC) tissues and corresponding adjacent normal tissues was detected by quantitative real-time PCR
Discussion miRNAs exert a biological function by targeting the 3′-untranslated region (3′-UTR) region of genes. Because this region regulates subcellular localization, nuclear transport and stabilizes transcripts[15], miRNAs play an important role in cells

Summary

Introduction

Esophageal cancer is the world’s eighth most malignant tumor and has a 5-year-survival rate of less than 15%1. More than 60% of human protein-coding genes are expected to be regulated by miRNAs4, which are involved in the development and progression of malignant tumors by acting on different target genes[5,6]. These genes play important roles in regulating cell differentiation, proliferation, invasion, apoptosis and angiogenesis[7,8,9]. The Notch signalling pathway is a highly conserved pathway that affects cell proliferation, differentiation, apoptosis, and adhesion and is closely related to embryonic development, angiogenesis and tumor formation. The results provide a new theoretical basis for diagnosing and treating ESCC

Methods

Results

Conclusion