J Cancer 2019; 10(24):6124-6134. doi:10.7150/jca.32511

Research Paper

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

Yaojun Peng1*, Li Wang2*, Liangliang Wu3, Ling Zhang2, Guangjun Nie4, Mingzhou Guo1✉

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.

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Citation:
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

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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.

Keywords: SLFN11, gastric cancer, epigenetics, methylation, DNA damage repair, cisplatin