PSMA1 mediates tumor progression and poor prognosis of gastric carcinoma by deubiquitinating and stabilizing TAZ

Abstract

The deubiquitinating enzyme family in tumor progression play important role in intracellular protein degradation. The proteasome subunit alpha type 1 (PSMA1) has been reported to act as an oncogene in several human cancers. The present study aimed to reveal the functional significance of PSMA1 in gastric cancer (GC) progression and the underlying mechanisms. The expression of PSMA1 in human GC samples and GC cell lines was examined by western blot analysis, real-time PCR, immunohistochemistry (IHC), and in vitro ubiquitination assays and established a xenograft mouse model. We found that PSMA1 was upregulated in GC and promoted proliferation, migration and invasion in GC cells. Herein, we report transcriptional co-activator with PDZ-binding motif (TAZ) was a downstream gene of PSMA1. Mechanistically, PSMA1 directly interacted with and stabilized TAZ via deubiquitination in GC. Furthermore, we found that TAZ was the essential mediator of PSMA1-modulated oncogenic activity in vitro and in vivo. Examination of clinical samples confirmed that elevated mediators of PSMA1, concomitant with increased TAZ abundance, correlate with human GC progression. These data suggested that PSMA1 promotes GC progression and proliferation by deubiquitinating TAZ. PSMA1 promotes GC progression and proliferation regarding PSMA1-mediated deubiquitinating enzyme activity and suggest potential therapeutic targets for GC management.

LINC00460 Promotes Cutaneous Squamous Cell Carcinoma Progression Through Stabilizing ELAVL1 Protein

“…The cell lysates were incubated overnight with Protein-A/G MagBeads (Yeasen, Shanghai, China) and anti-ELAVL1 antibody (Cell Signaling Technology) or normal rabbit IgG (Cell Signaling Technology) at 4 °C. The protein complexes were retrieved, washed, and subjected to western blotting with an anti-ubiquitin antibody (Cell Signaling Technology) [ 23 ].…”

Expression and DNA methylation of 20S proteasome subunits as prognostic and resistance markers in cancer

“…Several studies have reported alterations in the expression of single proteasome subunits in various types of cancer. PSMA1, a subunit of the 20S CP, has been found to be overexpressed and considered a prognostic or cancer marker in several tumors, including lung, gastric, breast and colon cancer [15][16][17][18]. Indeed, proteasome α-subunits have been associated with the development and progression of several types of cancers, including hepatocellular carcinoma, breast cancer, lung cancer, and multiple myeloma [19][20][21][22][23].…”