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Updated: Jun 7, 2025

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Immunosuppressive SOX9-AS1 Resists Triple-Negative Breast Cancer Senescence Via Regulating Wnt Signalling Pathway

Xuan Ye1, Yi Cen2, Quan Li1

  • 1Department of Breast and Thyroid Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, PR China.

Journal of Cellular and Molecular Medicine
|November 17, 2024
PubMed

Insights

SOX9-AS1, a long noncoding RNA, promotes triple-negative breast cancer by inhibiting senescence and Wnt signaling. Inhibiting SOX9-AS1 may enhance therapy-induced senescence and immune response in TNBC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Triple-negative breast cancer (TNBC) presents therapeutic challenges, partly due to resistance to therapy-induced senescence (TIS).
  • Long noncoding RNAs (lncRNAs) play roles in cancer progression and senescence regulation.
  • Identifying key senescence-related lncRNAs (SRlncRNAs) is crucial for developing novel TNBC treatment strategies.

Purpose of the Study:

  • To identify SRlncRNAs involved in TNBC senescence.
  • To investigate the role of SOX9-AS1 in TNBC cell growth, senescence, and immune infiltration.
  • To elucidate the molecular mechanism by which SOX9-AS1 affects TNBC.

Main Methods:

  • Bioinformatic mining of SRlncRNAs.
  • In vitro experiments using MDA-MD-231 TNBC cells.
  • Assessment of cell proliferation, apoptosis, migration, invasion, and senescence.
  • Analysis of Wnt signaling pathway components (GSK-3β/β-catenin).
  • Immune infiltration analysis.

Main Results:

  • Seven SRlncRNAs were identified, with SOX9-AS1 showing high expression in TNBC cells.
  • SOX9-AS1 knockdown inhibited TNBC cell growth and malignant phenotypes.
  • SOX9-AS1 knockdown promoted tamoxifen-induced senescence and senescence-associated secretory phenotype (SASP) factor transcription.
  • SOX9-AS1 resisted senescence by inhibiting Wnt signaling activation.
  • Low SOX9-AS1 expression correlated with increased infiltration of specific immune cells (naïve B cells, CD8+ T cells, γδ T cells).

Conclusions:

  • SOX9-AS1 promotes TNBC by resisting senescence through the Wnt signaling pathway.
  • Targeted inhibition of SOX9-AS1 enhances SASP and immune infiltration, offering a potential adjunct to TIS strategies for TNBC.
Keywords:
SOX9‐AS1Wnt signalling pathwayimmune infiltrationsenescencetriple‐negative breast cancer

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