Overexpression of FES might inhibit cell proliferation, migration, and invasion of osteosarcoma cells
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PRIMARY RESEARCH
Cancer Cell International Open Access
Overexpression of FES might inhibit cell proliferation, migration, and invasion of osteosarcoma cells Yang Zhao1†, Zhimeng Wang2†, Qian Wang1, Liang Sun1, Ming Li1, Cheng Ren1, Hanzhong Xue1, Zhong Li1, Kun Zhang1, Dingjun Hao1, Na Yang1, Zhe Song1, Teng Ma1* and Yao Lu1*
Abstract Background: 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. Methods: The 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-Aza2′-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. Results: A 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-AzaDC 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. Conclusions: The 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. Keywords: Osteosarcoma, Risk model, Prognosis, FES overexpression, Tumor suppressor Background Osteosarcoma (OS) is a type of bone malignancy. 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% *Correspondence: [email protected]; [email protected] † Yang Zhao and Zhimeng Wang contributed equally to this work 1 Department of Orthopaedic Surgery, Honghui Hospital, Xi’an Jiaotong University, No. 555 Youyi East Road, Xi’an 710054, Shaanxi, China Full list of author information is available at the end of the article
of pediatric tumors worldwide [2]. OS is characterized by the formation of vast immature bone or osteoid tissue, and is derived from mesenchymal stem cells or progenitor cells of osteoblast lineage [3]. Surgical resection followed by adjuvant chemotherapy is a typical method of OS treatment. Although many advancements have been made in OS
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