[PSMD11 overexpression promotes epithelial-mesenchymal transition in gastric cancer and affects patient prognosis].

OBJECTIVES

To investigate the expression of the 26S proteasome non-ATPase regulatory subunit 11 (PSMD11) in gastric cancer and its impact on long-term patient prognosis. Methods Tumor and adjacent tissue samples were collected from a cohort of 94 gastric cancer patients treated at our hospital from January, 2016 to December, 2019. Immunohistochemistry was used to detect PSMD11 and Ki67 expression levels in the tissues, whose correlations with clinicopathological parameters and postoperative 5-year survival of the patients were analyzed. PSMD11 expression in gastric cancer was also analyzed using data from the GEPIA and UALCAN databases, while the KM-plotter database was used to predict 5-year survival rates. KEGG and GO enrichment analyses were employed to predict the biological functions and mechanisms of PSMD11. In cultured HGC-27 cells, the effects of PSMD11 knockdown and overexpression on cell migration, invasion and expressions of epithelial-mesenchymal transition (EMT) markers and TGF‑β/Smad pathway proteins were evaluated using scratch wound healing assay, Transwell assay, and Western blotting.

RESULTS

Bioinformatic analysis showed that PSMD11 expression was significantly elevated in gastric cancer and positively correlated with Ki67 expression (r=0.73, P<0.05). Survival analysis suggested that high PSMD11 expression was correlated with a poorer prognosis in gastric cancer patients. Univariate and multivariate Cox regression analyses identified PSMD11 as an independent prognostic risk factor in gastric cancer (HR: 2.167, 95% CI: 1.159-4.051, P=0.015). Enrichment analysis suggested involvement of PSMD11 in EMT and TGF‑β signaling. In HGC-27 cells, PSMD11 overexpression significantly enhanced while PSMD11 knockdown suppressed cell migration and invasion. PSMD11 overexpression significantly increased the expression levels of vimentin, N-cadherin, TGF‑β, and p-Smad2/3 and reduced E-cadherin expression, and PSMD11 knockdown produced the opposite changes.

CONCLUSIONS

PSMD11 is overexpressed in gastric cancer and adversely affects patient prognosis likely by driving EMT via activation of the TGF-β/Smad signaling pathway.