The present study aimed to examine the association between hypoxia-inducible factor (HIF)-1α and the Wnt/β-catenin signaling pathway in a hypoxic environment. The study also aimed to explore the possible mechanisms underlying the invasion of hypoxic gastric cancer cells in vitro and in vivo. The pcDNA™ 6.2-GW/EmGFP-miR-β-catenin plasmid was transfected into SGC-7901 gastric cancer cells, resulting in cells with stable suppression of β-catenin expression. The biological characteristics of the control, liposome, negative control, β-catenin knockdown, hypoxia and hypoxia β-catenin knockdown groups were tested using an invasion assay. The differences in the invasive capacity of the control, negative control and liposome groups were not statistically significant. However, the hypoxia group demonstrated a significantly enhanced invasive capacity, as compared with that in the control group (P<0.05). In the hypoxia β-catenin knockdown group, reduced cell penetration and diminished invasive behavior was observed (P<0.05). In the hypoxia and double (chemical + physical) hypoxia groups, HIF-1α, β-catenin, urokinase-type plasminogen activator (uPA) and matrix metalloproteinase (MMP-7) protein and mRNA expression levels were elevated. In response to knockdown of β-catenin expression, HIF-1α, β-catenin, uPA and MMP-7 protein as well as mRNA expression levels were significantly reduced in the hypoxia β-catenin knockdown and the double hypoxia β-catenin knockdown groups. In an in vivo experiment, the growth rate of xenograft tumors of hypoxic and control cells was high alongside increased HIF-1α, β-catenin, uPA and MMP-7 levels according to western blot and immunohistochemical analyses, while growth and protein levels of tumors from hypoxic β-catenin knockdown cells were significantly lower and those of β-catenin knockdown cells were lowest. In conclusion, these results suggested that HIF-1α activation was able to regulate the Wnt/β-catenin pathway, and that HIF-1α may be controlled by the Wnt/β-catenin pathway. A potential mechanism underlying SGC-7901 tumorigenicity is the activation of the Wnt/β-catenin signaling pathway, which activates uPA and MMP-7 expression and contributes to the enhanced invasion of hypoxic cancer cells.

Globally, gastric cancer (GC) is the second most common malignancy of the digestive tract. 1 GC is the third and fifth most common cause of cancer-related deaths in men and women, respectively, with a relatively high incidence in China and East Asia. 1,2 In 2015, China reported approximately 470 000 new cases of GC and nearly 500 000 associated deaths. 3 Although a comprehensive antitumour pattern based on surgical resection and the combined use of targeted drugs and immunotherapy have improved the prognosis of patients with GC, their 5-year survival and overall survival (OS) rates are far from satisfactory. 4 It is well known that recurrent and distant metastases are the leading causes of death in patients with GC. Therefore, it is necessary to investigate the molecular mechanisms of GC progression and explore novel therapeutic targets. With the development of modern molecular biotechnology, the progression of cancer has been found to be closely associated with the activation of oncogenes and the inactivation of tumour suppressor genes. Keratin 18 (KRT18) is located on chromosome 12q13.13 and encodes the main component of epithelial

lncRNA Mirt2 is a lipopolysaccharide- (LPS-) inducible inflammation inhibitor. We found that Mirt2 was downregulated in plasma of ulcerative colitis (UC) patients and the downregulation of Mirt2 distinguished UC patients from healthy controls. IL-22 was also downregulated in UC patients and positively correlated with Mirt2. Mirt2 overexpression led to upregulated, while Mirt2 siRNA silencing led to inhibited secretion of IL-22 from colonic epithelial cells treated with LPS. In addition, under LPS treatment, Mirt2 overexpression led to decreased, while Mirt2 siRNA silencing led to increased apoptotic rate of colonic epithelial cells. Therefore, Mirt2 is downregulated in ulcerative colitis and regulates IL-22 expression in colonic epithelial cells.