Expression and role of V1A subunit of V-ATPases in gastric cancer cells.

Vacuolar-ATPases (V-ATPases) play an important role in maintaining a relatively neutral pHi (internal pH) and are responsible for the progression of cancer. V-ATPases contain different subunits and few studies have been conducted on subunit V1A. This study aimed to investigate the gene expression of V1A subunit of V-ATPases in gastric cancer tissues and explore its role in the progression and prognosis of gastric cancer. The protein expressions of the V1A subunit of V-ATPase gene in 100 normal gastric specimens and 100 gastric cancer tissues were determined by immunohistochemistry. The role of V1A subunit of V-ATPases was studied using a specific small interfering RNA (siRNA). The positive expression rate of the V1A subunit of V-ATPases was 76 % in gastric cancer tissue samples, much higher than that in normal tissue samples (30 %, P < 0.05), and was correlated with histological grade (P = 0.001), lymph node metastasis (P = 0.002), TNM (P = 0.040), and vascular invasion (P = 0.010), but not with patient age, sex, depth of tumor invasion, tumor size, or histological type. The median overall survival times of 76 patients who had positive staining for tumor cell V1A subunit of V-ATPases and 24 patients who had negative staining were 31.7 and 59.2 months, respectively. When the expression of V1A subunit was knocked down using siRNA, the proliferation and invasion of gastric cancer cells in vitro were significantly inhibited. V1A subunit of V-ATPases can be a prognostic indicator for poor outcome and is a therapeutic target in gastric cancer.