MiR-335-5p suppresses gastric cancer progression by targeting MAPK10

Yi Gao,Haiyan Shi,Jing Zhang,Juan Du,Ruxin Ding,Changan Zhao,Fenghui Wang,Yan Yao,Weihong Hu,Xiaofei Wang,Mengjie Zhang,Huahua Zhang,Chen Huang,Dan Li,Yun Feng,Jing Yan,Lumin Wang,Yanfeng Wang

doi:10.1186/s12935-020-01684-z

Abstract

BackgroundRecent studies have established the roles of microRNAs (miRNAs) in cancer progression. The aberrant expression of miR-335-5p has been reported in many cancers, including gastric cancer (GC). In this study, the precise roles of miR-335-5p in GC as well as the molecular mechanisms underlying its effects, including the role of its target MAPK10, were evaluated.MethodsQuantitative real-time PCR was used to evaluate miR-335-5p levels in GC cell lines and tissues. MTT and colony formation assays were used to detect cell proliferation, and Transwell and wound-healing assays were used to evaluate the invasion and migration of GC cells. The correlation between levels of miR-335-5p and the cell cycle-related target gene mitogen-activated protein kinase 10 (MAPK10) in GC was analyzed. In addition, the candidate target was evaluated by a luciferase reporter assay, qRT-PCR, and western blotting.ResultsThe levels of miR-335-5p were downregulated in GC tissues and cell lines. Furthermore, miR-335-5p inhibited the proliferation and migration of GC cells and induced apoptosis. Additionally, miR-335-5p arrested the cell cycle at the G1/S phase in GC cells in vitro. Levels of miR-335-5p and the cell cycle-related target gene MAPK10 in GC were correlated, and MAPK10 was directly targeted by miR-335-5p.ConclusionsThese data suggest that miR-335-5p is a tumor suppressor and acts via MAPK10 to inhibit GC progression.

Highlights

Recent studies have established the roles of microRNAs in cancer progression
Results miR‐335‐5p inhibits gastric cancer (GC) cell proliferation in vitro To investigate the role and function of miR-335-5p in GC cells, we analyzed its expression in 22 pairs of GC tissues and matched adjacent non-cancerous tissue samples by qRT-PCR. miR-335-5p levels were significantly lower in GC samples than in non-cancerous tissue samples (Fig. 1a)
These results were validated in five GC cell lines. miR-335-5p levels was lower in the BGC-823, SGC-7901, MKN-45, MKN-28, and AGS cell lines than in the GES-1 cell line (Fig. 1b)

Summary

Introduction

Recent studies have established the roles of microRNAs (miRNAs) in cancer progression. The aberrant expression of miR-335-5p has been reported in many cancers, including gastric cancer (GC). Over 1,000,000 new cases and an estimated 783,000 deaths were reported in 2018, making it the fifth most frequently diagnosed cancer and the Recent studies have established the important roles of microRNAs (miRNAs), which are small, non-proteincoding RNAs that regulate gene expression at the posttranscriptional level, in tumorigenesis [7,8,9]. MiR-335-5p is significantly downregulated and has a vital role in the metastasis of non-small cell lung cancer [16]. The downregulation of miR-335 in GC has been reported [19]; its precise roles in GC cells are not fully understood

Methods

Results

Conclusion