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30 May 2019 : Laboratory Research  

RNA-Binding Motif 4 (RBM4) Suppresses Tumor Growth and Metastasis in Human Gastric Cancer

Hongmei Yong12BE, Wei Zhao3BC, Xueyi Zhou2G, Zhenyun Liu4D, Qi Tang5F, Huichang Shi2F, Ronghui Cheng2C, Xiao Zhang5B, Zhenning Qiu5D, Jin Zhu56F, Zhenqing Feng157A*

DOI: 10.12659/MSM.914513

Med Sci Monit 2019; 25:4025-4034

Abstract

BACKGROUND: Dysregulation of the splicing activator, RNA-binding motif 4 (RBM4), has recently been reported to be involved in the progression of several cancers. However, the mechanisms that underpin the activity of RBM4 in gastric cancer (GC) remain unknown. The purpose of our study was to explore how RBM4 affects the biological behavior of GC through in vivo and in vitro experiments.

MATERIAL AND METHODS: Western blot and flow cytometry analyses were used to investigate the RBM4 protein levels in normal gastric epithelial cells and 5 types of GC cells. Cell Counting Kit-8 assay, flow cytometry analysis, wound-healing, and migration and invasion assays were evaluated in vitro in BGC823 and MGC803 GC cells. A xenograft tumor model was used to assess whether RBM4 inhibits GC growth in vivo. Mitogen-activated protein kinase (MAPK) protein levels were determined using western blot analyses.

RESULTS: Our study revealed that RBM4 protein was downregulated in GC cells. Re-expression of RBM4 inhibited the proliferation, migration, and invasion of GC cells, while promoting apoptosis. Thus, the overexpression of RBM4 can inhibit tumor growth in GC mouse models. We also report that RBM4 was involved in the activation of MAPK-dependent signaling pathways in human GC.

CONCLUSIONS: It is hoped that these findings will improve our understanding of GC pathogenesis while also helping us to explore the feasibility of RBM4-targeted therapy for GC treatment.

Keywords: Genes, Tumor Suppressor, Stomach Neoplasms, Cell Movement, Cell Proliferation, China, Disease Progression, Down-Regulation, Epithelial-mesenchymal transition, Gene Expression Regulation, Neoplastic, MicroRNAs, Neoplasm Invasiveness, RNA-Binding Motifs, RNA-Binding Proteins, Xenograft Model Antitumor Assays

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750