XEDAR inhibits the proliferation and induces apoptosis of gastric cancer cells by regulating JNK signaling pathway.

Lihong Yang,Feifei Ding,Wei Wang,Tao Jiang,Xiaojun Huang

doi:10.1042/bsr20192726

Lihong Yang, Feifei Ding + Show 3 more

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https://doi.org/10.1042/bsr20192726

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Journal: Bioscience reports	Publication Date: Dec 20, 2019
Citations: 4	License type: CC BY 4.0

Affiliation: Lanzhou University Second Hospital

Abstract

X-linked ectodermal dysplasia receptor (XEDAR) has been widely studied in epidermal morphogenesis, but few studies have been conducted on tumorigenesis and development, including gastric cancer. In the present research, we aimed to investigate the effect of XEDAR on gastric cancer and further explore the molecular mechanisms involved. The differential expression of XEDAR in 90 tissue specimens (30 gastric cancer tissues, 30 adjacent tissues and 30 normal tissues) was detected by real-time PCR (RT-PCR) and Western blot. Cell proliferation and apoptosis were explored using MTT and Annexin-V/propidium iodide (PI) assays, respectively. The results revealed that the expression of XEDAR was decreased in gastric cancer tissues and in gastric cancer cell lines, and its expression is regulated by p53 in BGC-823 cells. Furthermore, overexpression of XEDAR inhibited cell proliferation and induced apoptosis in BGC-823 cells. XEDAR moreover inhibited proliferation and induced apoptosis in gastric cancer cells by regulating the JNK signaling pathway. Collectively, the results of the present study suggested that XEDAR inhibits cell proliferation and induces apoptosis by participating in p53-mediated signaling pathway and inhibiting the downstream JNK signaling pathway in gastric cancer.

Highlights

Gastric cancer (GC) is one of the most common malignant tumours in China and Asia
Most X-linked ectodermal dysplasia receptor (XEDAR) was expressed on the cell membrane in gastritis tissues, while a small amount of XEDAR was expressed on the cell membrane or in the cytoplasm in gastric cancer tissues (Figure 1E)
As XEDAR has been identified as a target gene for p53 in embryonic fibroblasts [19], we further explored the effect of p53 on XEDAR expression in BGC-823 cells

Summary

Introduction

Gastric cancer (GC) is one of the most common malignant tumours in China and Asia. The incidence of GC ranks second among the most common malignant tumours with the highest morbidity and mortality in China [1]. Further understanding of the occurrence, development and metastasis of GC is of great importance for early detection, diagnosis, treatment and staging [2]. Functional changes in oncogenes and tumour suppressor genes play important roles in the development of GC [3,4]. It is an important task for many GC researchers to identify GC-related pathogenic genes so as to find new targets for the specific diagnosis and treatment of GC [5]

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