Int J Biol Sci 2021; 17(12):3145-3157. doi:10.7150/ijbs.59825 This issue

Research Paper

Inhibition of protein PMP22 enhances etoposide-induced cell apoptosis by p53 signaling pathway in Gastric Cancer

Jingjing Hou1,2,3*, Lin Wang1,2,3*, Jiabao Zhao1,2,3*, Huiqin Zhuo1,2,3*, Jia Cheng1,2,3, Xin Chen1,2,3, Wei Zheng1,2,3, Zhijun Hong1,2,3, Jianchun Cai1,2,3✉

1. Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian 361004, China
2. Institute of Gastrointestinal Oncology, Medical college of Xiamen University, Xiamen, Fujian 361004, China
3. Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen 361004, Fujian, China
*These authors contributed equally to the work.

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Citation:
Hou J, Wang L, Zhao J, Zhuo H, Cheng J, Chen X, Zheng W, Hong Z, Cai J. Inhibition of protein PMP22 enhances etoposide-induced cell apoptosis by p53 signaling pathway in Gastric Cancer. Int J Biol Sci 2021; 17(12):3145-3157. doi:10.7150/ijbs.59825. Available from https://www.ijbs.com/v17p3145.htm

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Abstract

Graphic abstract

Gastric Cancer (GC) is one of the main causes leading to death. PMP22, as a member of the GAS3 family of tetraspan proteins, it is associated with a variety of neurological diseases. Recently, more and more studies have shown that PMP22 play a great role in the physiological processes such as cells adhesion, migration, proliferation and tumorigenesis, but the involvement and functional mechanisms of PMP22 in Gastric carcinoma are not investigated clearly. In this study, we found that the PMP22 was overexpressed in the GC cells and tissue. Knockdown of PMP22 inhibits cell growth. Over-expressed PMP22 inhibits the etoposide-induced apoptosis, meanwhile knockdown of PMP22 promotes the etoposide-induced proliferation suppression, and increases cell apoptosis in GC cells. Furthermore, PMP22 enhanced the inhibition of the p53 transcriptional activities and down-regulated the p53 targeting genes, including p21, BAX and PUMA with or without treatment of etoposide. Finally, our results showed that PMP22 reduced the etoposide-induced tumor growth suppression in nude mice. Taken together, our research provided an anti-apoptotic properties alternative mechanism for PMP22 in gastric carcinoma and suggested PMP22 can be a potential target for the treatment of gastric cancer.

Keywords: PMP22, etoposide, p53, Apoptosis, gastric cancer