The Inhibition of B7H3 by 2-HG Accumulation Is Associated With Downregulation of VEGFA in IDH Mutated Gliomas

• DOI: 10.3389/fcell.2021.670145
• Publication Date: 2021-05-17T06:03:01Z
• Authors: Mengli Zhang; Huaichao Zhang; Minjie Fu; Jingwen Zhang; Cheng Zhang; Yingying Lv; Fengfeng Fan; Jinsen Zhang; Hao Xu; Dan Ye; Hui Yang; Wei Hua; Ying Mao
• Keywords: VEGFA; autophagy; Cell and Developmental Biology; 0303 health sciences; 03 medical and health sciences; QH301-705.5; glioma; B7H3; 2-HG; Biology (General); IDH mutation; 3. Good health

B7H3 (also known as CD276) is a co-stimulator checkpoint protein of the cell surface B7 superfamily. Recently, function beyond immune regulation has been widely studied. However, expression preference and mechanism underlying in different subtypes gliomas rarely understood. We show here that significantly decreased IDH-mutated cultured IDH1-R132H glioma cells. Accumulation 2-HG leads to remarkable downregulation activity mutant responsible for reduction Inhibition autophagy by inhibitors like leupeptin, chloroquine (CQ), Bafilomycin A1 (Baf-A1) blocks degradation In meantime, flux more active with higher LC3B-II lower p62 cells than IDH1-WT Furthermore, sequence alignment analysis reveals potential LC3-interacting region (LIR) motifs “F-V-S/N-I/V” B7H3. Moreover, interacts CQ treatment enhances this interaction. Additionally, we find positively correlated VEGFA MMP2 bioinformatics gliomas. are further reduced high compared low sections IHC staining. Our study demonstrates preferentially overexpressed IDH wild-type could serve theranostic target precise patients IDH.