J Cancer 2019; 10(24):6124-6134. doi:10.7150/jca.32511
Methylation of SLFN11 promotes gastric cancer growth and increases gastric cancer cell resistance to cisplatin
1. Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, #28 Fuxing Road, Beijing 100853, China
2. Department of Surgery, The Affiliated Cancer Hospital of Zhengzhou University, #127 Dongming Road, Zhengzhou, Henan Province 450008, China.
3. Department of Oncology, Chinese PLA General Hospital, #28 Fuxing Road, Beijing 100853, China.
4. CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, North Road No. 1, Zhongguancun, Beijing, 100190, China.
*These authors contributed equally to this work.
Peng Y, Wang L, Wu L, Zhang L, Nie G, Guo M. Methylation of SLFN11 promotes gastric cancer growth and increases gastric cancer cell resistance to cisplatin. J Cancer 2019; 10(24):6124-6134. doi:10.7150/jca.32511. Available from http://www.jcancer.org/v10p6124.htm
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.
Keywords: SLFN11, gastric cancer, epigenetics, methylation, DNA damage repair, cisplatin