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

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.

• Authors: Jingjing Hou, Lin Wang, Jiabao Zhao, Huiqin Zhuo, Jia Cheng, Xin Chen, Wei Zheng, Zhijun Hong, Jianchun Cai
• Journal: International journal of biological sciences (Int J Biol Sci) Vol. 17 Issue 12 Pg. 3145-3157 ( 2021) ISSN: 1449-2288 [Electronic] Australia
• PMID: 34421356 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The author(s).

Chemical References

• Antineoplastic Agents, Phytogenic
• Myelin Proteins
• PMP22 protein, human
• Pmp22 protein, mouse
• Trp53 protein, mouse
• Tumor Suppressor Protein p53
• Etoposide

Topics

• Animals
• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Etoposide (pharmacology)
• Female
• Flow Cytometry
• Gene Expression Regulation, Neoplastic (physiology)
• Humans
• Lentivirus (genetics)
• Male
• Mice
• Middle Aged
• Myelin Proteins (antagonists & inhibitors, genetics)
• Plasmids
• RNA Interference
• Real-Time Polymerase Chain Reaction
• Signal Transduction
• Stomach Neoplasms (drug therapy, metabolism, pathology)
• Transfection
• Tumor Suppressor Protein p53 (metabolism)
• Xenograft Model Antitumor Assays