SLFN11的甲基化促进胃癌生长并增加胃癌细胞对顺铂的耐药性。
Methylation of SLFN11 promotes gastric cancer growth and increases gastric cancer cell resistance to cisplatin.
作者信息
Peng Yaojun, Wang Li, Wu Liangliang, Zhang Ling, Nie Guangjun, Guo Mingzhou
机构信息
Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, #28 Fuxing Road, Beijing 100853, China.
Department of Surgery, The Affiliated Cancer Hospital of Zhengzhou University, #127 Dongming Road, Zhengzhou, Henan Province 450008, China.
出版信息
J Cancer. 2019 Oct 15;10(24):6124-6134. doi: 10.7150/jca.32511. eCollection 2019.
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. 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. 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 and and enhanced the ability of cisplatin to induce S-phrase arrest and apoptosis in gastric cancer cells. 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.
人类SLFN11基因编码一种与RNA解旋酶结构相似的蛋白质，据报道该蛋白质可使癌细胞对DNA损伤剂敏感。本研究探讨了SLFN11在人类胃癌中的表观遗传调控及其机制。分析了8种人类胃癌细胞系和201例原发性胃癌。采用甲基化特异性PCR、流式细胞术、异种移植小鼠模型和siRNA技术。在29.9%（60/201）的原发性胃癌中，SLFN11发生甲基化。SLFN11的表达受启动子区域甲基化调控。SLFN11甲基化与肿瘤大小显著相关（p<0.05）。SLFN11在体内和体外均能抑制胃癌生长，并增强顺铂诱导胃癌细胞S期阻滞和凋亡的能力。SLFN11在人类胃癌中经常发生甲基化，其表达受启动子区域甲基化调控。我们的结果表明，SLFN11是人类胃癌中的一种肿瘤抑制因子，SLFN11甲基化可能作为人类胃癌中顺铂耐药的标志物。
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