SOX2-OT induced by PAI-1 promotes triple-negative breast cancer cells metastasis by sponging miR-942-5p and activating PI3K/Akt signaling

Cell Mol Life Sci. 2022 Jan 7;79(1):59. doi: 10.1007/s00018-021-04120-1.

Abstract

Triple-negative breast cancer (TNBC) has an aggressive biological behavior and poor outcome. Our published study showed that PAI-1 could induce the migration and metastasis of TNBC cells. However, the underlying mechanism by which PAI-1 regulates TNBC metastasis has not been addressed. Here, we demonstrated that PAI-1 is high expressed in TNBC and promotes TNBC cells tumorigenesis. Using microarray analysis of lncRNA expression profiles, we identified a lncRNA SOX2-OT, which is induced by PAI-1 and could function as an oncogenic lncRNA in TNBC. Mechanistic analysis demonstrated that SOX2-OT acts as a molecular sponge for miR-942-5p to regulate the expression of PIK3CA, ultimately leading to activating PI3K/Akt signaling pathway and promoting TNBC metastasis. Taken together, our findings suggest that SOX2-OT regulates PAI-1-induced TNBC cell metastasis through miR-942-5p/PIK3CA signaling and illustrate the great potential of developing new SOX2-OT-targeting therapy for TNBC patients.

Keywords: LY294002; Lung and liver metastases; PAI-039; PAI-1/SERPINE1; ceRNA.

MeSH terms

  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / genetics
  • Class I Phosphatidylinositol 3-Kinases / biosynthesis
  • Class I Phosphatidylinositol 3-Kinases / metabolism*
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Metastasis / genetics
  • Plasminogen Activator Inhibitor 1 / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Long Noncoding / genetics*
  • Signal Transduction / genetics
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / pathology

Substances

  • MIRN942 microRNA, human
  • MicroRNAs
  • Plasminogen Activator Inhibitor 1
  • RNA, Long Noncoding
  • SERPINE1 protein, human
  • long non-coding RNA Sox2ot, human
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • Proto-Oncogene Proteins c-akt