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RGS12 represses oral squamous cell carcinoma by driving M1 polarization of tumor-associated macrophages via

Gongsheng Yuan1, Shuting Yang1, Shuying Yang2,3,4

  • 1Department of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, USA.

International Journal of Oral Science
|February 16, 2023
PubMed

Insights

Regulator of G protein signaling 12 (RGS12) drives antitumor function in tumor-associated macrophages (TAMs) by promoting M1 polarization. This discovery offers a new target for oral cancer therapy by reprogramming immunosuppressive TAMs.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Tumor-associated macrophages (TAMs) are critical in tumor progression and immune evasion.
  • Mechanisms to redirect TAMs towards antitumor functions are largely unknown.
  • Oral cancer progression involves complex immune interactions.

Purpose of the Study:

  • To investigate the role of Regulator of G protein signaling 12 (RGS12) in oral cancer.
  • To elucidate the mechanisms by which RGS12 influences TAM polarization and function.
  • To identify RGS12 as a potential biomarker and therapeutic target in oral cancer.

Main Methods:

  • Transcriptome profiling of human oral cancer tissues.
  • Analysis of RGS12 knockout mice models in oral cancer.
  • Investigation of RGS12 interactions with MYCBP2 and KIF2A in TAMs.

Main Results:

  • RGS12 was identified as a regulator of immune-related pathways in oral cancer.
  • RGS12 knockout in macrophages led to decreased M1 TAMs and increased oral cancer cell proliferation/invasion.
  • RGS12 promotes M1 macrophage polarization by activating MYCBP2 to degrade KIF2A, enhancing cilia.
  • RGS12 acts as a biomarker and regulator of immunosuppressive TAM activation.

Conclusions:

  • RGS12 is a key regulator of TAM polarization towards an antitumor M1 phenotype.
  • Targeting RGS12 could reprogram immunosuppressive TAMs for oral cancer treatment.
  • RGS12 represents a promising biomarker for oral cancer prognosis and therapeutic strategy.

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