Abstract
BACKGROUND: Chloride channel-3 (CLC-3) has been reported to promote the proliferation and invasion in various tumors, yet little is known about its role in gastric cancer. In the present study, we investigated the clinical significance of CLC-3 and its biological role in gastric cancer. METHODS: Bioinformatic analysis, immunohistochemical staining, quantitative real-time polymerase chain reaction and Western blot assay were used to assess the expression of CLC-3 and its clinical significance in gastric cancer. The biological role of CLC-3 and its underlying mechanism were detected through in vitro experiments. RESULTS: CLC-3 was highly expressed in gastric cancer tissues and cell lines, and high levels of CLC-3 were significantly associated with adverse clinicopathological parameters and shorter overall survival time in patients with gastric cancer. Functional studies revealed that silencing of CLC-3 decreased, while overexpression promoted, the proliferation, migration and invasion of gastric cancer cells in vitro. Mechanistic studies suggested that canonical TGF-β/Smad signaling pathway is involved in CLC-3-induced gastric cancer cells proliferation, migration and invasion. CONCLUSION: These findings indicate the vital role of CLC-3 in gastric cancer progression and its potential role of a therapeutic target for treatment.