GPX8 is transcriptionally regulated by FOXC1 and promotes the growth of gastric cancer cells through activating the Wnt
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Cancer Cell International Open Access
PRIMARY RESEARCH
GPX8 is transcriptionally regulated by FOXC1 and promotes the growth of gastric cancer cells through activating the Wnt signaling pathway Hong Chen1,2†, Lu Xu1†, Zhi‑li Shan2, Shu Chen3 and Hao Hu1*
Abstract Background: Glutathione Peroxidase 8 (GPX8) as a member of the glutathione peroxidase (GPx) family plays an important role in anti-oxidation. Besides, dysregulation of GPX8 has been found in gastric cancer, but its detailed molecular mechanism in gastric cancer has not been reported. Methods: Our study detected the expression of GPX8 in gastric cancer tissues and cell lines using immunohisto‑ chemistry (IHC), western blot and qRT-PCR, and determined the effect of GPX8 on gastric cancer cells using CCK-8, colony formation, transwell migration and invasion assays. Besides, the effect of GPX8 on the Wnt signaling pathway was determined by western blot. Furthermore, the transcription factor of GPX8 was identified by bioinformatics methods, dual luciferase reporter and chromatin immunoprecipitation (CHIP) assays. In addition, the effect of GPX8 on tumor formation was measured by IHC and western blot. Results: The over-expression of GPX8 was observed in gastric cancer tissues and cells, which facilitated the prolifera‑ tion, migration and invasion of gastric cancer cells as well as the tumor growth. GPX8 knockdown effectively inhibited the growth of gastric cancer cells and tumors. Moreover, GPX8 could activate the Wnt signaling pathway to promote the cellular proliferation, migration and invasion through. Furthermore, FOXC1 was identified as a transcription factor of GPX8 and mediated GPX8 expression to affect cell development processes. Conclusions: These findings contribute to understanding the molecular mechanism of GPX8 in gastric cancer. Addi‑ tionally, GPX8 can be a potential biomarker for gastric cancer therapy. Keywords: GPX8, FOXC1, Gastric cancer, Wnt signaling pathway Background Gastric cancer is one of the leading causes of cancerrelated death in the world [1]. The risk factors for gastric cancer mainly include Helicobacter pylori infection, unhealthy lifestyle (i.e. smoking, high consumption of salts, low intake of vegetables and fruits), and genetic *Correspondence: [email protected] † Hong Chen and Lu Xu contributed equally to this work. 1 Department of Gastrointestinal Surgery, The First Affiliated Hospital of Soochow University, No.899, Pinghai Road, Suzhou 215000, Jiangsu, China Full list of author information is available at the end of the article
alterations [2]. Up to now, surgical resection is an only curative therapy for locally gastric cancer at the early stage, and surgery combined with neoadjuvant or adjuvant therapy has been applied to treat locally advanced and metastatic disease [3]. Despite advances in the therapeutic methods, the patients have a poor prognosis with approximately 25% of the 5-year survival and about 1 year of median overall survival [4]. To improve the patient’s outcome, the targeted therapy has got more an
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