CircSOBP suppresses the progression of glioma by disrupting glycolysis and promoting the MDA5-mediated immune response

Maolin Mu; Wanxiang Niu; Fang Chu; Qingsheng Dong; Shanshan Hu; Chaoshi Niu

doi:10.1016/j.isci.2023.107897

CircSOBP suppresses the progression of glioma by disrupting glycolysis and promoting the MDA5-mediated immune response

iScience. 2023 Sep 13;26(10):107897. doi: 10.1016/j.isci.2023.107897. eCollection 2023 Oct 20.

Authors

Maolin Mu^{1

2}, Wanxiang Niu^{1

2}, Fang Chu^{1

2}, Qingsheng Dong^{1

2}, Shanshan Hu^{1

2

3

4}, Chaoshi Niu^{1

2

3

4}

Affiliations

¹ Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, P.R. China.
² Anhui Key Laboratory of Brain Function and Diseases, Hefei, Anhui 230001, P.R. China.
³ Anhui Provincial Stereotactic Neurosurgical Institute, Hefei, Anhui 230001, P.R. China.
⁴ Anhui Provincial Clinical Research Center for Neurosurgical Disease, Hefei, Anhui 230001, P.R. China.

Abstract

Glioma, an aggressively growing and highly malignant brain tumor, poses substantial therapeutic challenges due to its resistance to radiotherapy and chemotherapy. Recent research has identified circRNAs as pivotal players in glioma formation and development. However, the roles of circRNA in the metabolic and immune regulation of glioma are unclear. In this study, circSOBP expression was significantly downregulated in glioma cells and specimens. Functionally, enhanced circSOBP expression mitigated cell proliferation, invasion, migration, and glycolysis in gliomas. Mechanistically, circSOBP inhibited glycolysis and activated the MDA5-mediated IKKε/TBK1/IRF3 signaling pathway by binding TKFC proteins. Furthermore, the elevated levels of IFN-I induced by the MDA5 pathway increased the number and activity of CD8⁺ T and NK cells in the immune response of the animal models. In summary, our findings have emphasized the critical role of circSOBP in binding and modulating TKFC protein, offering potential therapeutic avenue for targeting glioma metabolism and immunological reprogramming.

Keywords: Biochemistry; Biological sciences; Cancer; Immunology; Molecular biology; Natural sciences.