Linc00152 promotes tumorigenesis by regulating DNMTs in triple-negative breast cancer

Biomed Pharmacother. 2018 Jan:97:1275-1281. doi: 10.1016/j.biopha.2017.11.055. Epub 2017 Dec 14.

Abstract

Long noncoding RNA (lncRNA) is a significant factor that regulates various aspects of genome activity, including tumor development and progression. Linc00152, a member of lncRNA, is unregulated in various types of cancer. However, its role in breast cancer, especially in triple-negative breast cancer (TNBC), is unclear. In this study, we found that linc00152 was highly expressed in all basal-like cell lines and in the majority of TNBC tissues. Linc00152 suppression by shRNA significantly inhibited invasion and colony growth. Such suppression also triggered apoptosis in vitro and inhibited tumor growth in vivo. We also revealed that linc00152 partially enhanced breast cancer tumorigenesis by inactivation of the BRCA1/PTEN through DNA methyltransferases. This study provides new insight regarding linc00152 as a promising biomarker and therapeutic target for human TNBC treatment.

Keywords: BRCA1; DNMTs; Linc00152; Long noncoding RNA; PTEN; Triple-negative breast cancer.

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Biomarkers, Tumor / metabolism
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • DNA Modification Methylases / genetics*
  • Female
  • Humans
  • Mice
  • Mice, Nude
  • PTEN Phosphohydrolase / genetics
  • RNA, Long Noncoding / genetics*
  • RNA, Small Interfering / genetics
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / pathology
  • Ubiquitin-Protein Ligases / genetics
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • long non-coding RNA Linc00152, human
  • DNA Modification Methylases
  • BRAP protein, human
  • Ubiquitin-Protein Ligases
  • PTEN Phosphohydrolase
  • PTEN protein, human