Abstract
The EF‑hand calcium binding protein tescalcin (TESC) is highly expressed in various human and mouse cancer tissues and is therefore considered a potential oncogene. However, the underlying mechanism that governs TESC expression remains unclear. Emerging evidence suggests that TESC expression is under epigenetic regulation. In the present study, the relationship between the epigenetic modification and gene expression of TESC in gastric cancer was investigated. To evaluate the relationship between the methylation and expression of TESC in gastric cancer, the methylation status of CpG sites in the TESC promoter was analyzed using microarray with the Illumina Human Methylation27 BeadChip (HumanMethylation27_270596_v.1.2), gene profiles from the NCBI Dataset that revealed demethylated status were acquired, and real‑time methylation‑specific PCR (MSP) in gastric cancer cells was conducted. In the present study, it was demonstrated that the hypermethylation of TESC led to the downregulation of TESC mRNA/protein expression. In addition, 5‑aza‑2c‑deoxycytidine (5'‑aza‑dC) restored TESC expression in the tested gastric cancer cells except for SNU‑620 cells. ChIP assay further revealed that the methylation of the TESC promoter was associated with methyl‑CpG binding domain protein (MBD)1, histone deacetylase (HDAC)2, and Oct‑1 and that treatment with 5'‑aza‑dC facilitated the dissociation of MBD1, HDAC2, and Oct‑1 from the promoter of TESC. Moreover, silencing of TESC increased MBD1 expression and decreased the H3K4me2/3 level, thereby causing transcriptional repression and suppression of cell survival in NCI‑N87 cells; conversely, overexpression of TESC downregulated MBD1 expression and upregulated the H3K4me2 level associated with active transcription in SNU‑638 cells. These results indicated that the differential expression of TESC via the modification status of the promoter and histone methylation controled cell survival in gastric cancer cells. Overall, the present study provided a novel therapeutic strategy for gastric cancer.