Abstract
BACKGROUND: Aberrant methylation in DNA regulatory regions could downregulate tumor suppressor genes without changing the sequences. However, our knowledge of secreted protein acidic and rich in cysteine (SPARC) and its aberrant methylation in gastric cancer (GC) is still inadequate. In the present research, we performed fundamental research to clarify the precise function of methylation on SPARC and its significance in GC. AIM: To investigate promoter methylation and the effects of the SPARC gene in GC cells and tissues and to evaluate its clinical significance. METHODS: Plasmids that overexpressed the SPARC gene were transfected into human GC BGC-823 cells; non-transfected cells were used as a control group (NC group). Quantitative real-time polymerase chain reaction and western blotting (WB) were then used to detect the expression of SPARC. Methylation-specific polymerase chain reaction was executed to analyze the gene promoter methylation status. Cell viability was measured by the cell counting kit-8 assay. The migration and invasion ability of cells were detected by scratch assays and transwell chamber assays, respectively. Cell cycle events and apoptosis were observed with a flow cytometer. RESULTS: The expression of SPARC mRNA in GC tissues and cells was significantly lower and showed differing degrees of hypermethylation, respectively, than that in normal adjacent tissues and control cells. Treatment with 5-Aza-2'-deoxycytidine (5-Aza-Cdr) was able to restore the expression of SPARC and reverse promoter hypermethylation. Overexpression of the SPARC gene significantly inhibited proliferation, migration, and invasion of GC cells, while also causing cell cycle arrest and apoptosis; the NC group exhibited the opposite effects. CONCLUSION: This study demonstrated that SPARC could function as a tumor suppressor and might be silenced by promoter hypermethylation. Furthermore, in GC cells, SPARC inhibited migration, invasion, and proliferation, caused cell cycle arrest at the G(0)/G(1) phase, and promoted apoptosis.