Long noncoding RNA linc00617 exhibits oncogenic activity in breast cancer

Mol Carcinog. 2017 Jan;56(1):3-17. doi: 10.1002/mc.22338. Epub 2015 Jul 24.

Abstract

Protein-coding genes account for only 2% of the human genome, whereas the vast majority of transcripts are noncoding RNAs including long noncoding RNAs. LncRNAs are involved in the regulation of a diverse array of biological processes, including cancer progression. An evolutionarily conserved lncRNA TUNA, was found to be required for pluripotency of mouse embryonic stem cells. In this study, we found the human ortholog of TUNA, linc00617, was upregulated in breast cancer samples. Linc00617 promoted motility and invasion of breast cancer cells and induced epithelial-mesenchymal-transition (EMT), which was accompanied by generation of stem cell properties. Moreover, knockdown of linc00617 repressed lung metastasis in vivo. We demonstrated that linc00617 upregulated the expression of stemness factor Sox2 in breast cancer cells, which was shown to promote the oncogenic activity of breast cancer cells by stimulating epithelial-to-mesenchymal transition and enhancing the tumor-initiating capacity. Thus, our data indicate that linc00617 functions as an important regulator of EMT and promotes breast cancer progression and metastasis via activating the transcription of Sox2. Together, it suggests that linc00617 may be a potential therapeutic target for aggressive breast cancer. © 2015 Wiley Periodicals, Inc.

Keywords: breast cancer; cancer stem-like cells; epithelial-mesenchymal-transition; linc00617; long noncoding RNA.

MeSH terms

  • Breast / metabolism
  • Breast / pathology*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Oncogenes
  • RNA, Long Noncoding / genetics*
  • Up-Regulation*

Substances

  • RNA, Long Noncoding
  • long noncoding RNA linc00617, human