Long non-coding RNA SOX21-AS1 enhances the stemness of breast cancer cells via the Hippo pathway

FEBS Open Bio. 2021 Jan;11(1):251-264. doi: 10.1002/2211-5463.13015. Epub 2020 Dec 1.

Abstract

Breast cancer stem cells (BCSCs) have high tumorigenicity and invasiveness, which contributes to recurrence and metastasis. The long non-coding RNA SOX21-AS1 has been previously reported to modulate the properties of breast cancer stem cells via targeting SOX2, although the underlying molecular mechanisms remain unclear. To investigate this issue, we first confirmed that the expression level of SOX21-AS1 is increased in breast cancer tissues and cell lines (MCF-7, MDA-MB-231, CSC-MCF-7, CSC-MDA-MB-231), especially in BCSCs. We demonstrated that SOX21-AS1 promotes the stemness of CSC-MCF-7 cells through western blot detection of stemness-related proteins, as well as side population and sphere formation assays. Overexpression of SOX21-AS1 enhanced the proliferation, migration and invasion of CSC-MCF-7 cells. We also observed that SOX21-AS1 inhibited the Hippo pathway. SOX21-AS1 enhanced the stemness, migration and invasion of CSC-MCF-7 cells by increasing the nuclear localization of YAP and decreasing the level of pYAP. Overall, we conclude that SOX21-AS1 may promote the stemness viability, proliferation, migration and invasion of BCSCs by inhibiting the Hippo pathway. Our findings provide insights into potential biomarkers and prognostic measures for the treatment of breast cancer.

Keywords: Hippo pathway; breast cancer stem cell; lncRNA SOX21-AS1; migration; proliferation; stemness.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Breast / pathology
  • Breast / surgery
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / surgery
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Hippo Signaling Pathway / genetics*
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • RNA, Long Noncoding / metabolism*

Substances

  • Biomarkers, Tumor
  • RNA, Long Noncoding
  • long noncoding RNA SOX21-AS1, human