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Knockdown of TRIM65 suppressed the proliferation and invasiveness of gastric cancer cells by restricting the ubiquitin degradation of PPM1A.

Abstract
Gastric cancer is a type of serious malignant tumors all around the world. TCGA data showed that the expression of TRIM65 (E3 ubiquitin ligase) was enhanced in the gastric cancer tissues. The role of TRIM65 in the tumorigenesis of gastric cancer remains unclear. In this study, we successfully established TRIM65-knockdown gastric cancer cells. Next, CCK-8, colony formation assays and transwell assays were performed to detect the cell proliferation and invasion. The results showed that suppression of TRIM65 inhibited the proliferation and invasion of gastric cancer cells. Interestingly, the Western blot assay confirmed that downregulation of TRIM65 increased the level of PPM1A and decreased the level of p-TBK1 in gastric cancer cells. Mechanistically, immunoprecipitation assay revealed that knockdown of TRIM65 inhibited the ubiquitin degradation of PPM1A. In rescue experiments, suppression of PPM1A promoted the proliferation and invasion of gastric cancer cells transfected with sh-TRIM65. Therefore, our results suggested that knockdown of TRIM65 inhibited the proliferation and invasion of gastric cancer cells by suppressing the ubiquitin degradation of PPM1A and phosphorylation of TBK1.
AuthorsChang Liu, Weiping Sun, Kui Yang, Boning Xia
JournalExperimental cell research (Exp Cell Res) Vol. 416 Issue 2 Pg. 113154 (07 15 2022) ISSN: 1090-2422 [Electronic] United States
PMID35421368 (Publication Type: Journal Article)
CopyrightCopyright © 2022 Elsevier Inc. All rights reserved.
Chemical References
  • Tripartite Motif Proteins
  • Ubiquitin
  • Ubiquitin-Protein Ligases
  • PPM1A protein, human
  • Protein Phosphatase 2C
  • TRIM65 protein, human
Topics
  • Cell Line, Tumor
  • Cell Movement (genetics)
  • Cell Proliferation (genetics)
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasm Invasiveness (genetics)
  • Protein Phosphatase 2C (metabolism)
  • Stomach Neoplasms (genetics)
  • Tripartite Motif Proteins (genetics, metabolism)
  • Ubiquitin (metabolism)
  • Ubiquitin-Protein Ligases (genetics, metabolism)

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