Journal
ONCOTARGET
Volume 8, Issue 48, Pages 84285-84299Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.20894
Keywords
ATP1B3; proliferation; apoptosis; migration; gastric cancer
Categories
Funding
- National Natural Science Foundation of China [81470303]
- Jiangsu Province Natural Science Foundation of China [BK20141140]
- Natural Science Research Projects in the Universities in Jiangsu province [14KJB320021]
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ATP1B3 encodes the beta 3 subunit of Na+/K+-ATPase and is located in the q22-23 region of chromosome 3. Na+/K+-ATPase participates in normal cellular activities but also plays a crucial role in carcinogenesis. In the present study, we found that expression of the beta 3 subunit of NNa+/K+-ATPase was increased in human gastric cancer tissues compared with that in normal matched tissues and that this increased expression predicted a poor outcome. ATP1B3 expression was elevated at both the mRNA and protein levels in gastric cancer cell lines relative to those in a normal gastric epithelial cell line. Interestingly, ATP1B3 knockdown significantly inhibited cell proliferation, colony-formation ability, migration, and invasion and increased apoptosis in human gastric carcinoma cell lines. Additionally, knockdown induced cell cycle arrest at the G2/M phase. Furthermore, we demonstrated that ATP1B3 silencing decreased the expression of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) and phosphorylated AKT (p-AKT), indicating that ATP1B3 regulates gastric cancer cell progression via the PI3K/AKT signalling pathway. Hence, the beta 3 subunit of Na+/K+-ATPase plays an essential role in the tumourigenesis of gastric cancer and may be a potential prognostic and therapeutic target for the treatment of gastric cancer.
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