KEY TAKEAWAYS
- The study aimed to explore how USP9X and MTH1 regulate proliferation, survival, migration, and invasion in gastric cancer cells.
- The results showed that USP9X stabilizes MTH1, enhancing proliferation, survival, migration, and invasion in gastric cancer cells.
MutT homolog 1 (MTH1) sanitizes oxidized dNTP pools to aid cancer cell survival and is often upregulated in cancers. Polyubiquitination stabilizes MTH1, promoting melanoma cell proliferation, indicating that the ubiquitin system regulates MTH1 stability and function. However, the role of ubiquitination in regulating MTH1 in gastric cancers remains unclear.
Wenji Xu and the team aimed to examine how USP9X interacts with MTH1 to regulate the proliferation, survival, migration, and invasion of gastric cancer cells.
The study evaluated the interaction between USP9X and MTH1 using co-immunoprecipitation (co-IP) in HGC-27 gastric cancer cells. Researchers used siRNAs to disrupt USP9X expression in HGC-27 and MKN-45 gastric cancer cell lines. They assessed cell proliferation with MTT assays, analyzed the cell cycle with propidium iodide (PI) and 7-AAD staining, examined apoptosis with Annexin V/PI staining, and measured migration and invasion using transwell assays. These tests were conducted on control, USP9X-deficient, and USP9X-deficient plus MTH1-overexpressing HGC-27 and MKN-45 cells.
The results showed that USP9X interacts with and deubiquitinates MTH1. Overexpressing USP9X increases MTH1 protein levels by reducing its ubiquitination, while knocking down USP9X has the opposite effect. USP9X deficiency in HGC-27 and MKN-45 cells leads to reduced proliferation, cell cycle arrest, increased apoptosis, and impaired migration and invasion, which can be rescued by overexpressing MTH1.
The study concluded that USP9X interacts with and stabilizes MTH1, enhancing the proliferation, survival, migration, and invasion of gastric cancer cells.
Funding was provided by the Natural Science Foundation of Fujian Province of China, Science and Technology Project of Quanzhou, China, and Youth Research Project of Fujian Health Commission.
Source: https://pubmed.ncbi.nlm.nih.gov/39075342/
Xu W, Zhang Y, Su Y, et al. (2024). “USP9X regulates the proliferation, survival, migration and invasion of gastric cancer cells by stabilizing MTH1.” BMC Gastroenterol. 2024;24(1):239. Published 2024 Jul 29. doi:10.1186/s12876-024-03321-9
