Methylation of SLFN11 promotes gastric cancer growth and increases gastric cancer cell resistance to cisplatin

Abstract

Background and Aim: Human SLFN11 gene encodes a protein with structural similarity to RNA helicases, which was reported to sensitize cancer cells to DNA-damaging agents. This study explored the epigenetic regulation and mechanism of SLFN11 in human gastric cancer. Methods: Eight human gastric cancer cell lines and 201 cases of primary gastric cancer were analyzed. Methylation specific PCR, flow cytometry, xenograft mouse model and siRNA technique were employed. Results: SLFN11 was methylated in 29.9% (60/201) of primary gastric cancer. The expression of SLFN11 was regulated by promoter region methylation. Methylation of SLFN11 was significantly associated with tumor size (p < 0.05). SLFN11 suppressed gastric cancer growth both in vitro and in vivo and enhanced the ability of cisplatin to induce S-phrase arrest and apoptosis in gastric cancer cells. Conclusions: SLFN11 is frequently methylated in human gastric cancer, and its expression is regulated by promoter region methylation. Our results demonstrate that SLFN11 is a tumor suppressor in human gastric cancer, and methylation of SLFN11 may serve as a cisplatin resistant marker in human gastric cancer.