[High expression of CDKN3 promotes migration and invasion of gastric cancer cells by regulating the p53/NF-κB signaling pathway and inhibiting cell apoptosis].

OBJECTIVES

To investigate the expression of CDKN3 in gastric cancer and its impact on prognosis of gastric cancer patients.

METHODS

We analyzed CDKN3 expression in clinical specimens from 114 gastric cancer patients and assessed its association with 5-year postoperative survival of the patients. GO and KEGG enrichment analyses were used to predict the biological function and possible mechanism of CDKN3. The effects of lentivirus-mediated CDKN3 knockdown on biological behaviors of gastric cancer cells were evaluated using Transwell assay, CCK-8 assay, TUNEL staining, flow cytometry, and Western blotting.

RESULTS

CDKN3 expression was significantly higher in gastric cancer tissues than in the adjacent tissues with significant correlations with CEA level, CA19-9 level, and T and N staging (<0.05). High CDKN3 expression was an independent risk factor affecting 5-year postoperative survival of the patients and predictive for long-term prognosis (<0.01). Enrichment analyses suggested a probable association of CDKN3 with apoptosis. In MGC-803 cells, CDKN3 knockdown significantly lowered migration and invasion capacities of the cells, while CDKN3 overexpression produced the opposite effects. TUNEL staining revealed a significantly lower level of cell apoptosis in gastric cancer tissues than in adjacent tissues (<0.01). CDKN3 knockdown obviously inhibited proliferation and increased apoptosis of MGC-803 cells. CDKN3 overexpression down-regulated the expressions of p53, p21 and Bax and up-regulated the expressions of p-p65 and Bcl-2.

CONCLUSIONS

CDKN3 is highly expressed in gastric cancer tissues and affects patient prognosis. CDKN3 overexpression promotes proliferation, invasion and migration and suppressed apoptosis of gastric cancer cells possibly through the p53/NF-κB signaling pathway.