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Original Article | Open Access

RGS12 represses oral squamous cell carcinoma by driving M1 polarization of tumor-associated macrophages via controlling ciliary MYCBP2/KIF2A signaling

Gongsheng Yuan1 , Shuting Yang1, Shuying Yang1,2,3 ( )
Department of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, USA
The Penn Center for Musculoskeletal Disorders, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
Center for Innovation & Precision Dentistry, Penn Dental Medicine and School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, USA
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Abstract

Tumor-associated macrophages (TAMs) play crucial roles in tumor progression and immune responses. However, mechanisms of driving TAMs to antitumor function remain unknown. Here, transcriptome profiling analysis of human oral cancer tissues indicated that regulator of G protein signaling 12 (RGS12) regulates pathologic processes and immune-related pathways. Mice with RGS12 knockout in macrophages displayed decreased M1 TAMs in oral cancer tissues, and extensive proliferation and invasion of oral cancer cells. RGS12 increased the M1 macrophages with features of increased ciliated cell number and cilia length. Mechanistically, RGS12 associates with and activates MYC binding protein 2 (MYCBP2) to degrade the cilia protein kinesin family member 2A (KIF2A) in TAMs. Our results demonstrate that RGS12 is an essential oral cancer biomarker and regulator for immunosuppressive TAMs activation.

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International Journal of Oral Science
Volume 15,
2023
Article number: 11
DOI: 10.1038/s41368-023-00216-5

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Yuan G, Yang S, Yang S. RGS12 represses oral squamous cell carcinoma by driving M1 polarization of tumor-associated macrophages via controlling ciliary MYCBP2/KIF2A signaling. International Journal of Oral Science, 2023, 15: 11. https://doi.org/10.1038/s41368-023-00216-5

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Received: 26 April 2022
Revised: 13 December 2022
Accepted: 20 December 2022
Published: 16 February 2023
© The Author(s) 2023

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