DNA Methylation-Mediated Silencing of Regenerating Protein 1 Alpha (REG1A) Affects Gastric Cancer Prognosis

BACKGROUND: Gastric cancer (GC) is one of the most common cause of cancer-related deaths. The clinical trials still lack the effective methods to treat or monitor the disease progression. In this research, the biological function and the underlying molecular mechanism of regenerating protein 1 alpha (REG1A) in GC were investigated.
MATERIAL AND METHODS: Gene expression omnibus (GEO), KMplot datasets and GC tissue microarray (n=164) were used to analyze the expression of REG1A and related patient prognoses in GC. Transwell matrigel assay, flow cytometry analysis and CCK8 cell viability assay were performed to detect the biological functions of REG1A. Western blotting and real-time PCR were used to detect the REG1A expression and PI3K/Akt related signaling.
RESULTS: It was found that the expression of REG1A was significantly downregulated in GC and closely related with clinicopathological findings or patient prognoses. REG1A overexpression could suppress the invasion, cell viability and promote the apoptosis of GC cells. Moreover, we found that the epigenetic methylation suppressed the expression level of REG1A in GC, and REG1A overexpression could suppress the phosphorylation of Akt or GSK3β signaling.
CONCLUSIONS: Taken together, REG1A regulates cell invasion, apoptosis and viability in GC through activating PI3K/Akt-GSK3β signaling. REG1A may serve as a promising therapeutic strategy for GC.

Keywords: Apoptosis, Neoplasm Invasiveness, Stomach Neoplasms