Aberrant methylation of secreted protein acidic and rich in cysteine gene and its significance in gastric cancer

Abstract

BACKGROUNDAberrant 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.AIMTo investigate promoter methylation and the effects of the SPARC gene in GC cells and tissues and to evaluate its clinical significance.METHODSPlasmids 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.RESULTSThe 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.CONCLUSIONThis 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 G0/G1 phase, and promoted apoptosis.

Potential Prognostic Role of SPARC Methylation in Non-Small-Cell Lung Cancer

“…In support of our in vitro studies, the same inverse correlation between the hypermethylation of CpGs of SPARC promoter and its transcript levels was observed by analyzing 450K methylation array data for the CpG of SPARC for an independent cohort of 877 LUADs and 765 LUSC of TCGA dataset. Together, our data corroborate the link between methylation and expression of SPARC just observed in many other solid tumors [ 33 , 34 ].…”

SPARC: a potential target for functional nanomaterials and drugs

“…Subsequently, clinical studies have found that SPARC is a possible marker for diagnosing and prognosticating gastric cancer and an important factor regulating various signaling pathways (Wang et al, 2019). The SPARC gene acts to suppress epigenetic tumorigenesis (Shao, 2018). SPARC brings new targets and therapies to treat gastric cancer (Zhou, 2018).…”