RAE1 promotes gastric carcinogenesis and epithelial-mesenchymal transition.

Wenhui Dong, Xiaofei Li, Lulu Cheng, Jing Yang, Ziyan Zhao, Xihui Qiang, Pengmei Li, Ju Wu, Lianyi Guo

Archives of biochemistry and biophysics 2024 Apr

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The purpose of this study was to explore the role of RAE1 in the invasion and metastasis of gastric cancer (GC) cells. RAE1 expression in GC cells was determined by reverse-transcription polymerase chain reaction (qRT-PCR) and Western blotting (WB). Cell models featuring RAE1 gene silencing and overexpression were constructed by lentiviral transfection; The proliferation, migration, and invasion ability of cells were detected by cell counting, colony formation assay, would healing assay, and transwell invasion and migration test. WB analysis of ERK/MAPK signaling pathway (ERK1/2, p-ERK1/2, c-Myc) and EMT-related molecules (ZEB1, E-cadherin, N-cadherin, and Vimentin). The expression level of RAE1 in GC was notably higher than in adjacent tissues. Elevated RAE1 expression correlated with an unfavorable prognosis for GC patients. Knockdown of RAE1, as compared to the control group, resulted in a significant inhibition of proliferation, migration, and invasion abilities in GC cell lines. Furthermore, RAE1 knockdown led to a substantial decrease in the expression of N-cadherin, vimentin, ZEB1, p-ERK1/2, and c-Myc proteins, coupled with a marked increase in E-cadherin expression. The biological effects of RAE1 in GC cells were effectively reversed by the inhibition of the ERK/MAPK signaling pathway using SCH772984. Additionally, RAE1 knockdown demonstrated a suppressive effect on GC tumor size in vivo. Immunohistochemistry (IHC) results revealed significantly lower expression of Ki-67 in RAE1 knockout mice compared to the control group. RAE1 promotes GC cell migration and invasion through the ERK/MAPK pathway and is a potential therapeutic target for GC therapy. Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Wenhui Dong, Xiaofei Li, Lulu Cheng, Jing Yang, Ziyan Zhao, Xihui Qiang, Pengmei Li, Ju Wu, Lianyi Guo. RAE1 promotes gastric carcinogenesis and epithelial-mesenchymal transition. Archives of biochemistry and biophysics. 2024 Apr;754:109896