Abstract

Recent evidence shows that miRNAs are dysregulated in a variety of cancers including gastric cancer (GC), and emerging as key oncogenes or tumor suppressors. In this study, qRT-PCR was used to analyze the expression of miR-186 in GC tissues and adjacent non-cancerous tissues, and then more in-vitro experiments were used to investigate the role of miR-186 in GC cells. Here, we identified miR-186 was generally down-regulated in GC tissues; however, Twist1 was generally up-regulated in GC tissues. Moreover, miR-186 and Twist1 were associated with larger tumor size and advanced clinical stage of GC. In-vitro experiments demonstrated that ectopic overexpression of miR-186 inhibited GC cell proliferation, invasion and migration; however, inhibited expression of miR-186 enhanced cell proliferation, invasion and migration. Furthermore, the luciferase reporter assay demonstrated Twist1 as a direct target of miR-186. Finally, over-expression of Twist1 abrogated inhibitory impact of miR-186 on cell proliferation, invasion and migration. In conclusion, miR-186 affects the proliferation, invasion and migration of human gastric cancer by inhibition of Twist1, and could be a tumor suppressor in GC development. Thus, miR-186 may be served as a candidate prognostic biomarker and target for new therapies in human gastric cancer.

Highlights

  • There is an obvious decrease in the prevalence of gastric cancer, gastric cancer still acts as the second one in the most common malignancies in the real world, especially in China [1, 2]

  • These findings indicated that miR-186 and Twist1 might be involved in the development of gastric cancer

  • Emerging evidence demonstrated that dysregulation of expression of miRNAs in gastric cancer might be thought as one of the leading factors in tumorigenesis, and miRNAs can be recommended as a predictive biomarker in the diagnosis of gastric cancer patients

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Summary

Introduction

There is an obvious decrease in the prevalence of gastric cancer, gastric cancer still acts as the second one in the most common malignancies in the real world, especially in China [1, 2]. The common metastasis and recurrence have been reported as the main rationales, which affect the long-term survival of postoperative gastric cancer patients [3]. A large quantity of oncogenes and tumor suppressors has been reported to be involved in the regulation of the development of GC. MiRNAs have the capacity of regulating the gene expression by targeting the 3'-untranslated regions (UTR) of related mRNAs in the development of different tumors [4, 5]. It has been reported that miR-186 has a wide role in regulation of some functions involving suppression of cancer cell proliferation and inhibition of organ metastasis of different cancers. Little is known about the role of miR-186 in the development of GBM

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