Overexpression of FES might inhibit cell proliferation, migration, and invasion of osteosarcoma cells

Yang Zhao,Zhimeng Wang,Dingjun Hao,Qian Wang,Liang Sun,Hanzhong Xue,Zhong Li,Zhe Song,Teng Ma,Na Yang,Cheng Ren,Yao Lu,Kun Zhang,Ming Li

doi:10.1186/s12935-020-01181-3

Yang Zhao, Zhimeng Wang + Show 12 more

Open Access

https://doi.org/10.1186/s12935-020-01181-3

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Abstract

BackgroundThis study aimed to screen osteosarcoma (OS) prognosis relevant genes for methylation dysregulation, and the functional mechanisms of FES overexpression in OS cells were investigated.MethodsThe OS prognosis relevant genes with differentially methylated positions (DMPs) identified from the GSE36001 and GSE36002 datasets, and the UCSC database, were used as a training set to construct a risk model, while the GSE21257 dataset was used as validation set. The expression levels of several key genes in OS cells after 5-Aza-2′-deoxycytidine treatment were detected by qPCR. The effects of FES overexpression on cell proliferation, cell cycle, migration, and invasion of MNNG/HOS were analyzed by CCK8, flow cytometry, and Transwell assays.ResultsA total of 31 candidate genes, corresponding to 36 DMPs, were identified as OS prognosis relevant genes; from these, the top 10 genes were used to construct a risk model. Following validation of the risk model, FES, LYL1, MAP4K1, RIPK3, SLC15A3, and STAT3 showed expression changes between the OS and control samples. qPCR results showed that the expression of FES was significantly downregulated in three OS cell lines and increased after 5-Aza-DC treatment. The proliferation, cell cycle progression, migration, and invasion of MNNG/HOS cells were significantly inhibited after transfection with FES overexpression plasmid, and the protein expression of FYN and β catenin were decreased in MNNG/HOS cells by FES overexpression.ConclusionsThe decrease in FES by hypermethylation was associated with OS prognosis, and might contribute to the proliferation, migration, and invasion of OS cells. FES, and its upstream FYN and β catenin, might coordinately exert a tumor suppressor effect in OS cells.

Highlights

This study aimed to screen osteosarcoma (OS) prognosis relevant genes for methylation dysregulation, and the functional mechanisms of FES overexpression in OS cells were investigated
The probes in GSE36001 were totally annotated into 19,569 genes, and above 501 Differentially methylated position (DMP) were matched to 401 genes
The correlation analysis showed that only 130 DMPs were significantly negatively correlated with 114 genes, and these genes were considered candidate genes for future analysis

Summary

Introduction

This study aimed to screen osteosarcoma (OS) prognosis relevant genes for methylation dysregulation, and the functional mechanisms of FES overexpression in OS cells were investigated. Most diagnoses occur in children and adolescents, with a higher incidence males [1]. It is the sixth most common cancer in children and accounts for up about 3%. Gene methylation, an important component of epigenetics research, has been implicated the development, progression, and prognosis of OS [5, 6]. A significant decrease in the levels of SFRP2 mRNA and protein, induced by hypermethylation, have been detected in OS cells, which promotes OS invasion through activating Wnt signaling [8]. HOTAIR that inhibits the methylation level of CDKN2A, is reported to regulate OS cell viability through the HOTAIR-miR126-DNMT1-CDKN2A axis [9]

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