LINC00473 mediates cyclin D1 expression through a balance between activation and repression signals in breast cancer cells

FEBS Lett. 2019 Apr;593(7):751-759. doi: 10.1002/1873-3468.13353. Epub 2019 Mar 18.

Abstract

Long noncoding RNAs (lncRNAs) are critical regulators in tumorigenesis. However, their roles in breast cancer remain unclear. Here, we found that lncRNA LINC00473 is significantly upregulated in breast cancer cells. Loss- or gain-of-function experiments show that LINC00473 promotes cell proliferation. Mechanistically, LINC00473 is required for the activation of cyclin D1 (CCND1) expression through recruitment of phosphorylated CREB and histone acetylation to the CCND1 promoter. Interestingly, we found that LINC00473 is also required for maintaining the expression levels of the noncoding RNACCND1 s and recruiting corepressor FUS to the CCND1 promoter. Altogether, the activation effect of LINC00473 on CCND1 is a net effect of two antagonistic regulatory pathways. Our finding provides a novel lncRNA-mediated precise transcriptional control of CCND1.

Keywords: FUS; CCND1; LINC00473; breast cancer; ncRNACCND1s.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cyclin D1 / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Promoter Regions, Genetic
  • RNA, Long Noncoding / genetics*
  • RNA-Binding Protein FUS / genetics*
  • Transcriptional Activation / genetics

Substances

  • CCND1 protein, human
  • FUS protein, human
  • LINC00473 RNA, human
  • RNA, Long Noncoding
  • RNA-Binding Protein FUS
  • Cyclin D1