IDH1 mutation produces R-2-hydroxyglutarate (R-2HG) and induces mir-182-5p expression to regulate cell cycle and tumor formation in glioma

• DOI: 10.1186/s40659-024-00512-2
• Publication Date: 2024-05-17T09:01:44Z
• Authors: Haiting Zhao; Li Meng; Peng Du; Xinbin Liao; Xin Mo; Mengqi Gong; Jiaxin Chen; Yiwei Liao
• Keywords: CS-NPs(antagomir-182-5p); 0301 basic medicine; QH301-705.5; Brain Neoplasms; miR-182-5p; Glioma; R-2HG; Cell cycle; IDH1 mutation; Isocitrate Dehydrogenase; Mice; MicroRNAs; 03 medical and health sciences; Gliomas; Humans; Animals; Heterografts; Biology (General); Neoplasm Transplantation; Research Article

Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 IDH2), are present most gliomas. IDH1 mutation is an important prognostic marker glioma. However, its regulatory mechanism glioma remains incompletely understood. miR-182-5p expression was increased within IDH1-mutant specimens according to TCGA, CGGA, online dataset GSE119740, as well collected clinical samples. (R)-2-hydroxyglutarate ((R)-2HG) treatment up-regulated the of miR-182-5p, enhanced cell proliferation, suppressed apoptosis; inhibition partially eliminated oncogenic effects R-2HG upon cells. By direct binding Cyclin Dependent Kinase Inhibitor C (CDKN2C) 3'UTR, inhibited CDKN2C expression. Regarding cellular functions, knockdown promoted R-2HG-treated viability, apoptosis, relieved cycle arrest. Furthermore, attenuated on phenotypes. Moreover, exerted opposite check point apoptosis markers those inhibition; also, functions markers. The engineered CS-NPs (antagomir-182-5p) effectively encapsulated delivered antagomir-182-5p, enhancing anti-tumor efficacy vivo, indicating therapeutic potential CS-NPs(antagomir-182-5p) targeting miR-182-5p/CDKN2C axis against R-2HG-driven oncogenesis mice models. These insights highlight target axis, offering a promising avenue R-2HG's influence