MAGI2-AS3 inhibits breast cancer by downregulating DNA methylation of MAGI2

J Cell Physiol. 2021 Feb;236(2):1116-1130. doi: 10.1002/jcp.29922. Epub 2020 Jul 30.

Abstract

Breast cancer is one of the most threatening diseases for women. Long noncoding RNAs were reported to be involved in breast cancer development. In this study, we analyzed The Cancer Genome Atlas breast cancer tissue high-throughput sequencing data and screened and validated the low-expressing long noncoding RNA named MAGI2-AS3. Through gene coexpression analysis, we found that MAGI2-AS3 has a good expression correlation with MAGI2. Overexpression of MAGI2-AS3 or MAGI2 in breast cancer cells MCF-7 would inhibit the Wnt/β-catenin pathway and inhibit cell proliferation and migration. Gene structure and DNA methylation analysis results indicated that MAGI2-AS3 may act as a cis-acting regulatory element downregulating the DNA methylation level of the MAGI2 promoter region, and the DNA demethylase TET1 inhibitor can reverse MAGI2-AS3 overexpression caused upregulation of MAGI2 and cellular effects. Our findings reveal the role of MAGI2-AS3 in breast cancer and provide potential novel therapeutic targets for metastatic breast cancer intervention.

Keywords: DNA methylation; MAGI2; MAGI2-AS3; breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Movement
  • Cell Proliferation / genetics
  • DNA Methylation / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Guanylate Kinases / genetics*
  • Humans
  • MCF-7 Cells
  • Mixed Function Oxygenases / genetics*
  • Neoplasm Metastasis
  • Proto-Oncogene Proteins / genetics*
  • RNA, Long Noncoding / genetics*
  • Wnt Signaling Pathway

Substances

  • Adaptor Proteins, Signal Transducing
  • Proto-Oncogene Proteins
  • RNA, Long Noncoding
  • Mixed Function Oxygenases
  • TET1 protein, human
  • Guanylate Kinases
  • MAGI2 protein, human