LncRNA AY343892 inhibits breast cancer development by positively regulating BRCA1-mediated transcription of PTEN

Histol Histopathol. 2020 Oct;35(10):1171-1180. doi: 10.14670/HH-18-245. Epub 2020 Aug 5.

Abstract

Breast cancer remains a major challenge despite dramatic advances in cancer research. The long non-coding RNA (lncRNA) has been reported to associate with carcinogenesis and progression of various cancers. In this research, we found that lncRNA AY343892 was significantly down-regulated in breast cancer tissues and cells. Besides, breast cancer patients with high AY343892 level exhibited a favorable prognosis. Functional assays indicated that overexpression of AY343892 significantly inhibited proliferation and promoted apoptosis in breast cancer cells. In terms of mechanism, PTEN and BRCA1 were confirmed to be regulated by AY343892 in breast cancer. Luciferase activity and chromatin immunoprecipitation (ChIP) assays indicated that AY343892 can regulate the promoter of PTEN by binding to BCRA1. Further investigation suggested that knockdown of AY343892 significantly promoted MDA-MB-231 cell proliferation and inhibited MDA-MB-231 cell apoptosis. However, these effects were reversed when PTEN was up-regulated. Moreover, PTEN silence can also countervail the inhibitory effect of overexpressed BCRA1 or AY343892 on the expressions of genes related to proliferation and apoptosis in breast cancer. In conclusion, this study illustrated that AY343892 inhibited breast cancer development by positively regulating BRCA1-mediated transcription of PTEN. This finding contributes to a better understanding in the pathogenesis of breast cancer and provides a theoretical basis for the treatment of breast cancer patients.

MeSH terms

  • Apoptosis
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • BRCA1 Protein / genetics
  • BRCA1 Protein / metabolism*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MCF-7 Cells
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction
  • Transcription, Genetic

Substances

  • Apoptosis Regulatory Proteins
  • BRCA1 Protein
  • BRCA1 protein, human
  • Cell Cycle Proteins
  • RNA, Long Noncoding
  • PTEN Phosphohydrolase
  • PTEN protein, human