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The abnormal expression of the chicken ovalbumin upstream promoter transcription factor 2 (COUP-TFII) is associated with numerous forms of cancer, including gastric, prostate, colon and lung cancer. However, previous studies investigating the association between COUP-TFII expression and the occurrence, recurrence, invasion and metastasis of gastric cancer are limited in number. In the present study, it was revealed that the expression of COUP-TFII is significantly reduced in gastric carcinoma tissues compared with normal gastric mucosa cells (GES-1). In addition, the expression of COUP-TFII was also reduced in gastric cancer cell lines compared with GES-1 cells. Furthermore, it was revealed that ectopic expression of COUP-TFII was able to suppress the proliferation, migration and invasion of gastric cells, as well as inhibit hepatic metastasis, in vivo. In addition, it was demonstrated that COUP-TFII knockdown was able to promote the proliferation, migration and invasion of GES-1 cells in vitro. Furthermore, database analysis suggested that COUP-TFII expression in patients with gastric cancer is correlated with clinical stage classification and increased expression levels of COUP-TFII improved overall survival rates in patients with gastric cancer. The results of the present study suggest that COUP-TFII functions as a significant regulatory suppressor of gastric cancer growth and metastasis, and suggests that COUP-TFII may serve as a novel diagnostic and prognostic biomarker for gastric cancer metastasis.

NLRP6, a member of the Nod-like receptor family, protects against chemically induced intestinal injury and colitis-associated colon cancer. However, the cellular mechanisms involved in this NLRP6-mediated protection remain unclear. Here, we show that NLRP6 was down-regulated in approximately 75% of primary gastric cancer cases and exhibited significant associations with advanced clinical-stage lymph node metastasis and poor overall survival. Functional studies established that ectopic overexpression or down-regulation of NLRP6 inhibited cancer cell proliferation by inducing cell cycle arrest at the G1 phase via P21 and Cyclin D1 both in vitro and in vivo. Activation of the P14ARF-P53 pathway played a crucial role in the observed cellular senescence. We further demonstrated that ectopic overexpression of NLRP6 combined with inactivation of NF-κB(p65) and Mdm2 activates P14ARF-P53 to promote the senescence of gastric cancer cells. These findings indicate that NLRP6 functions as a negative regulator of gastric cancer and offer a potential new option for preventing gastric cancer.

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