Promotive effect and possible mechanism of high-mobility group protein A2 on invasion and metastasis of gastric cancer cells

Abstract

Objective To detect the expression of high-mobility group protein A2 (HMGA2) in gastric cancer tissues, investigate its relationship with clinicopathological features and prognosis, and explore its role and underlying mechanism in regulating the invasion and proliferation of gastric cancer cells. Methods TCGA database, GTEx database and bioinformatics analysis tools (GEPIA, KM plotter) were used to analyze the expression of HMGA2 gene in gastric cancer and the survival time of patients. The expression of HMGA2 protein in gastric cancer and adjacent tissues was detected by immunohistochemistry, and the correlation between HMGA2 expression and the clinicopathological parameters and its effect on prognosis of gastric cancer patients were analyzed. After HMGA2 was knocked down in gastric cancer cell line MGC-803, and overexpressed in gastric cancer cell line SGC-7901, plate cloning and transwell assay were used to detect the proliferation and invasion ability, respectively. The invasion ability was detected again in the HMGA2 overexpressed SGC-7901 cells after knockdown of Snail1. Western blotting was employed to measure the expression changes of HMGA2 and epithelial to mesenchymal transition (EMT) markers in the cells. Results The bioinformatics analysis showed that the mRNA expression of HMGA2 was significantly increased in gastric cancer tissues compared with normal gastric tissues (P < 0.05). Immunohistochemistry also indicated that the protein level of HMGA2 was obviously higher in gastric cancer tissues than para-cancer tissues, and it was associated with TNM staging, lymph node metastasis and survival rate. The gastric cancer patients with high HMGA2 expression had statistically shorter total survival and relapse-free survival (P < 0.05). Knockdown of HMGA2 resulted in decreased proliferation and invasion ability in MGC-803 cells decreased (P < 0.05), while its overexpression led to enhanced proliferation and invasion ability in SGC-7901 cells (P < 0.05). However, knocking down Snail1 would cause the invasion of HMGA2-overexpressed SGC-7901 cells reduced (P < 0.05), and the expression level of E-cadherin up-regulated and those of N-cadherin and Vimentin down-regulated. Conclusion High HMGA2 expression is associated with poor prognosis of gastric cancer patients, and it may promote invasion and metastasis of gastric cancer cells by regulating Snail1.

Keywords

• gastric cancer
• high-mobility group protein a2
• epithelial to mesenchymal transition
• snail1
• bioinformatics