1. Academic Validation
  2. Distinct Ring1b complexes defined by DEAD-box helicases and EMT transcription factors synergistically enhance E-cadherin silencing in breast cancer

Distinct Ring1b complexes defined by DEAD-box helicases and EMT transcription factors synergistically enhance E-cadherin silencing in breast cancer

  • Cell Death Dis. 2021 Feb 19;12(2):202. doi: 10.1038/s41419-021-03491-4.
Yawei Wang 1 Yingying Sun 1 Chao Shang 1 Lili Chen 1 Hongyu Chen 1 Dake Wang 1 Xianlu Zeng 2
Affiliations

Affiliations

  • 1 The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, Changchun, Jilin, China.
  • 2 The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, Changchun, Jilin, China. zengx779@nenu.edu.cn.
Abstract

Ring1b is a core subunit of polycomb repressive complex 1 (PRC1) and is essential in several high-risk cancers. However, the epigenetic mechanism of Ring1b underlying breast Cancer malignancy is poorly understood. In this study, we showed increased expression of Ring1b promoted metastasis by weakening cell-cell adhesions of breast Cancer cells. We confirmed that Ring1b could downregulate E-cadherin and contributed to an epigenetic rewiring via PRC1-dependent function by forming distinct complexes with DEAD-box RNA helicases (DDXs) or epithelial-mesenchymal transition transcription factors (EMT TFs) on site-specific loci of E-cadherin promoter. DDXs-Ring1b complexes moderately inhibited E-cadherin, which resulted in an early hybrid EMT state of epithelial cells, and EMT TFs-Ring1b complexes cooperated with DDXs-Ring1b complexes to further repress E-cadherin in mesenchymal-like Cancer cells. Clinically, high expression of Ring1b with DDXs or EMT TFs predicted low levels of E-cadherin, metastatic behavior, and poor prognosis. These findings provide an epigenetic regulation mechanism of Ring1b complexes in E-cadherin expression. Ring1b complexes may be potential therapeutic targets and biomarkers for diagnosis and prognosis in invasion breast Cancer.

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