YY1-regulated LINC00152 promotes triple negative breast cancer progression by affecting on stability of PTEN protein

Biochem Biophys Res Commun. 2019 Feb 5;509(2):448-454. doi: 10.1016/j.bbrc.2018.12.074. Epub 2018 Dec 26.

Abstract

Thousands of lncRNAs have been identified but few have been functionally characterized in triple negative breast cancer (TNBC). LINC00152 was known as cytoskeleton regulator RNA (CYTOR) and expressed in various cancers including breast cancer. But the underlying molecular mechanism of LINC00152 in pathogenesis of TNBC have not been elucidated. In our study, we identified that LINC00152 expression was dramatically elevated in TNBC tissue and cells. Inhibition or overexpression of LINC00152 obviously increased or suppressed PTEN protein expression but did not affect the mRNA expression level. Our further experiments showed up-regulated LINC00152 in TNBC obviously enhanced NEDD4-1 mediated ubiquitination and degradation of PTEN protein. Finally, we demonstrated that YY1 bound with LINC00152 promotor and mostly inhibited the transcription of LINC00152. Furthermore, analysis of clinical samples resource retrieved from databases suggested high LINC00152 expression was correlated with ER or PR negative expression, late TNM stage and lymphatic invasion, as well as shorter overall survival time in patients. Consequently, this study firstly reveals that up-regulated LINC00152 mediates PTEN protein stability attenuation in TNBC.

Keywords: LINC00152; PTEN; Triple negative breast cancer; Tumor progression; YY1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • Lymphatic Metastasis
  • Nedd4 Ubiquitin Protein Ligases / genetics
  • Nedd4 Ubiquitin Protein Ligases / metabolism
  • PTEN Phosphohydrolase / genetics*
  • PTEN Phosphohydrolase / metabolism
  • Protein Binding
  • Protein Stability
  • Proteolysis
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Signal Transduction
  • Survival Analysis
  • Triple Negative Breast Neoplasms / diagnosis
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / mortality
  • Triple Negative Breast Neoplasms / pathology
  • Ubiquitination
  • YY1 Transcription Factor / genetics*
  • YY1 Transcription Factor / metabolism

Substances

  • RNA, Long Noncoding
  • YY1 Transcription Factor
  • YY1 protein, human
  • long non-coding RNA Linc00152, human
  • Luciferases
  • Nedd4 Ubiquitin Protein Ligases
  • Nedd4 protein, human
  • PTEN Phosphohydrolase
  • PTEN protein, human