Knockdown of long non-coding RNA MAP3K20 antisense RNA 1 inhibits gastric cancer growth through epigenetically regulating miR-375

被引:33
作者
Quan, Yongsheng [1 ,2 ]
Zhang, Yan [3 ]
Lin, Wei [4 ]
Shen, Zhaohua [1 ,2 ]
Wu, Shuai [1 ,2 ]
Zhu, Changxin [1 ,2 ]
Wang, Xiaoyan [1 ,2 ]
机构
[1] Cent S Univ, Xiangya Hosp 3, Dept Gastroenterol, Tongzipo Rd 138, Changsha 410013, Hunan, Peoples R China
[2] Hunan Key Lab Nonresolving Inflammat & Canc, Changsha, Hunan, Peoples R China
[3] Cent S Univ, Xiangya Hosp 3, Dept Ultrasound, Changsha, Hunan, Peoples R China
[4] Cent S Univ, Xiangya Hosp, Dept Pathol, Changsha, Hunan, Peoples R China
关键词
Gastric cancer; Long non-coding RNA; Prognostic factor; MLK7-AS1; miR-375; Epigenetic; MICRORNA-375; CARCINOGENESIS; EXPRESSION; RECEPTOR; PDK1;
D O I
10.1016/j.bbrc.2018.02.072
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Emerging evidence has demonstrated that long noncoding RNAs (lncRNAs) play a critical role in tumorigenesis of gastric cancer. LncRNA MAP3K20 antisense RNA 1 (MLK7-AS1) has been identified as one of gastric cancer-specific lncRNAs. However, its precise role in gastric cancer remains unknown. In this study, we found that lncRNA MLK7-AS1 was significantly increased in gastric cancer tissues compared with in adjacent tissues. Gastric cancer patients with high MLK7-AS1 expression had a shorter survival and poorer prognosis. By loss-function assay, we demonstrated that knockdown of MLK7-AS1 inhibited cell proliferation and induced apoptosis in HGC27 and MKN-45 cells. Furthermore, we identified miR-375 as a target of MLK7-AS1. MLK7-AS1 interacted with Dnmt1 and recruited it to miR-375 pro motor, hyper-methylating miR-375 promotor and repressing miR-375 expression. Taken together, our findings demonstrate that knockdown of MLK7-AS1 by siRNA inhibits gastric cancer growth by epigenetically regulating miR-375. Thus, MLK7-AS1 may be a useful prognostic marker and therapeutic target for gastric cancer patients. (C) 2018 Elsevier Inc. All rights reserved.
引用
收藏
页码:527 / 534
页数:8
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