Elevated Expression of RPA3 Is Involved in Gastric Cancer Tumorigenesis and Associated with Poor Patient Survival.

Background: The replication protein A3 (RPA3) is a component of the RPA protein complex, which plays an essential role in multiple processes of DNA metabolism.

Aims: However, the involvement of RPA3 in gastric cancer tumorigenesis has not yet been investigated.

Methods: We stably knocked down RPA3 expression using short hairpin RNA in AGS cell line, and performed cell growth, colony formation and soft agar assays. Xenograft experiments were performed to examine tumor promoting properties of RPA3 in vivo. The qRT-PCR and immunohistochemistry were performed to evaluate RPA3 expression levels in 37 and 12 pairs of gastric cancer patient samples, respectively. Association between RPA3 expression and survival was evaluated in an independent cohort of 85 gastric cancer patients.

Results: Downregulation of RPA3 inhibited cell growth, clonogenicity and soft agar growth in AGS cells. Decreased expression of RPA3 significantly reduced tumor growth rate in AGS xenografts. In addition, RPA3 was upregulated in cancerous tissues compared with matched noncancerous adjacent tissues in gastric cancer patients. High expression of RPA3 was associated with poor patient survival.

Conclusion: Upregulation of RPA3 is involved in gastric cancer tumorigenesis and is associated with poorer patient survival. RPA3 represents a new therapeutic target of gastric cancer and serves as a potential prognostic biomarker for patient survival in gastric cancer.