MIER3 induces epithelial-mesenchymal transition and promotes breast cancer cell aggressiveness via forming a co-repressor complex with HDAC1/HDAC2/Snail

Exp Cell Res. 2021 Sep 1;406(1):112722. doi: 10.1016/j.yexcr.2021.112722. Epub 2021 Jul 6.

Abstract

Breast cancer is one of the most frequently diagnosed cancers and the leading cause of cancer death in women. MIER3 (Mesoderm induction early response 1, family member3) is considered as a potential oncogene for breast cancer. However, the role of MIER3 in breast cancer remain largely unknown. The expression of MIER3 was detected and the relationship between its expression and clinicopathological characteristics was also analyzed. The effect of MIER3 on proliferation and migration of breast cancer cells was detected in vitro and in vivo. Western blot, IF, and Co-IP were employed to detect the relationship between MIER3, HDAC1, HDAC2, and Snail. ChIP assay was performed to determine the binding of MIER3/HDAC1/HDAC2/Snail complex to the promoter of E-cadherin. In this study, we found that MIER3 was upregulated in breast cancer tissue and closely associated with poor prognosis of patients. MIER3 could promote the proliferation, migration, and epithelial-mesenchymal transition (EMT) of breast cancer cells. Further studies showed that MIER3 interacted with HDAC1/HDAC2 and Snail to form a repressive complex which could bind to E-cadherin promoter and was related to its deacetylation. Our study concluded that MIER3 was involved in forming a co-repressor complex with HDAC1/HDAC2/Snail to promote EMT by silencing E-cadherin.

Keywords: Breast cancer; EMT; HDAC; MIER3; Snail.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Histone Deacetylase 1 / genetics*
  • Histone Deacetylase 1 / metabolism
  • Histone Deacetylase 2 / genetics*
  • Histone Deacetylase 2 / metabolism
  • Humans
  • Mice
  • Mice, Nude
  • Middle Aged
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction / genetics
  • Snail Family Transcription Factors / genetics*
  • Snail Family Transcription Factors / metabolism
  • Survival Analysis
  • Tumor Burden
  • Xenograft Model Antitumor Assays

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • MIER3 protein, human
  • Nuclear Proteins
  • RNA, Small Interfering
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • HDAC1 protein, human
  • HDAC2 protein, human
  • Histone Deacetylase 1
  • Histone Deacetylase 2