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

Biochem Biophys Res Commun. 2018 Mar 4;497(2):527-534. doi: 10.1016/j.bbrc.2018.02.072. Epub 2018 Feb 8.

Abstract

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 HGC27and 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 promotor, 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.

Keywords: Epigenetic; Gastric cancer; Long non-coding RNA; MLK7-AS1; Prognostic factor; miR-375.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Epigenesis, Genetic
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Mice, Nude
  • MicroRNAs / genetics*
  • Middle Aged
  • RNA, Long Noncoding / genetics*
  • Stomach / pathology*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology

Substances

  • MIRN375 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding