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.
Int J Oral Sci. 2023 Feb 16;15(1):11. doi: 10.1038/s41368-023-00216-5.
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.
肿瘤相关巨噬细胞（TAMs）在肿瘤进展和免疫反应中发挥着关键作用。然而，驱动 TAMs 发挥抗肿瘤功能的机制尚不清楚。本研究通过对人口腔癌组织的转录组谱分析表明，G 蛋白信号调节因子 12（RGS12）调控病理性过程和免疫相关途径。巨噬细胞中 RGS12 敲除的小鼠口腔癌组织中 M1 型 TAMs 减少，口腔癌细胞广泛增殖和侵袭。RGS12 增加了具有纤毛细胞数量和纤毛长度增加特征的 M1 巨噬细胞。在机制上，RGS12 与 MYC 结合蛋白 2（MYCBP2）结合并使其激活，从而在 TAMs 中降解纤毛蛋白驱动蛋白家族成员 2A（KIF2A）。我们的研究结果表明，RGS12 是口腔癌的一个重要的生物标志物和免疫抑制性 TAMs 激活调节剂。
