Growth arrest-specific transcript 5 represses endometrial cancer development by promoting antitumor function of

Jiajie Tu1,2, Xuewen Tan2, Yu Chen1

  • 1Department of Gynecology, Shenzhen Second People's Hospital/The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China.

Cancer Science
|May 10, 2022
PubMed

Insights

Long noncoding RNA GAS5 suppresses endometrial cancer by reprogramming tumor-associated macrophages. GAS5 enhances macrophage anti-tumor activity, inhibiting cancer growth through immune modulation.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Long noncoding RNA (lncRNA) GAS5 is a known tumor suppressor.
  • The role of GAS5 in endometrial cancer (EC) and tumor-associated macrophages (TAMs) is unclear.

Purpose of the Study:

  • To investigate the function of GAS5 in TAMs within the context of endometrial cancer.
  • To elucidate the molecular mechanisms by which GAS5 influences TAM phenotype and anti-tumor activity.

Main Methods:

  • Quantitative PCR to assess GAS5 expression in EC tissues and TAMs.
  • Co-culture experiments of GAS5-overexpressing TAMs and EC cells.
  • In vivo tumor formation studies in immunodeficient mice.
  • Analysis of immune cell activation, phagocytosis, and signaling pathways (miR-21-PTEN-AKT, YAP1).

Main Results:

  • GAS5 expression was reduced in EC tissues and TAMs.
  • GAS5 overexpression in TAMs enhanced phagocytosis, antigen presentation, and T cell activation while reducing "Don't eat me" signals.
  • GAS5-overexpressing macrophages inhibited EC formation in vivo.
  • GAS5 promoted M1 TAM polarization by activating the miR-21-PTEN-AKT pathway and inhibiting YAP1.

Conclusions:

  • GAS5 acts as a tumor suppressor in endometrial cancer by modulating TAMs.
  • GAS5 transforms TAMs from a protumor to an antitumor phenotype, enhancing innate and adaptive immunity against EC.
  • The miR-21-PTEN-AKT pathway and YAP1 are key mediators of GAS5's anti-tumor effects in TAMs.

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