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Background Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2), are present in most gliomas. IDH1 mutation is an important prognostic marker in glioma. However, its regulatory mechanism in glioma remains incompletely understood. Results miR-182-5p expression was increased within IDH1-mutant glioma specimens according to TCGA, CGGA, and online dataset GSE119740, as well as collected clinical samples. (R)-2-hydroxyglutarate ((R)-2HG) treatment up-regulated the expression of miR-182-5p, enhanced glioma cell proliferation, and suppressed apoptosis; miR-182-5p inhibition partially eliminated the oncogenic effects of R-2HG upon glioma cells. By direct binding to Cyclin Dependent Kinase Inhibitor 2 C (CDKN2C) 3'UTR, miR-182-5p inhibited CDKN2C expression. Regarding cellular functions, CDKN2C knockdown promoted R-2HG-treated glioma cell viability, suppressed apoptosis, and relieved cell cycle arrest. Furthermore, CDKN2C knockdown partially attenuated the effects of miR-182-5p inhibition on cell phenotypes. Moreover, CDKN2C knockdown exerted opposite effects on cell cycle check point and apoptosis markers to those of miR-182-5p inhibition; also, CDKN2C knockdown partially attenuated the functions of miR-182-5p inhibition in cell cycle check point and apoptosis markers. The engineered CS-NPs (antagomir-182-5p) effectively encapsulated and delivered antagomir-182-5p, enhancing anti-tumor efficacy in vivo, indicating the therapeutic potential of CS-NPs(antagomir-182-5p) in targeting the miR-182-5p/CDKN2C axis against R-2HG-driven oncogenesis in mice models. Conclusions These insights highlight the potential of CS-NPs(antagomir-182-5p) to target the miR-182-5p/CDKN2C axis, offering a promising therapeutic avenue against R-2HG's oncogenic influence to glioma.
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Objective To study the correlation between microvessel density (MVD),isocitrate dehydrogenase 1 (IDH1) mutation and the malignancy of glioma,and its clinic significance.Methods The data and specimens of 40 patients with gliomas confirmed by surgery and pathology were collected.The relation between IDH1 mutation (detected by genetic sequence),MVD (detected by immunohistochemical coloration) and the malignancy of glioma was explored.5 cases of normal human brain tissues were used for comparative study.Results In normal brain tissue,Ⅰ,Ⅱ,Ⅲ,Ⅳ glioma,MVD counts were 8.12±1.64,25.10±1.27,27.00±1.98,42.80±10.75 and 56.50±5.23,respectively,and the overall difference was statistically significant (H =35.42,P ＜ 0.05).The MVD counts in low-grade glioma (Ⅰ-Ⅱ) and high-grade glioma (Ⅲ-Ⅳ) were 23.94±8.03 and 45.54±8.19,respectively,and the difference was statistically significant (t =-8.369,P ＜ 0.001).No mutation was found in normal human brain tissue,while in 20 cases of glioma specimens,there was IDH1 mutation with R132 as the mutation site and a MVD count of 31.11±13.47,and the other 20 cases of glioma specimens experienced no IDH1 mutation and the corresponding MVD count was 40.54±12.11.The difference of MVD counts of low-grade glioma and high-grade glioma was statistically significant (t =2.328,P=0.025).Conclusion MVD can be used as one of the histopathological grading metrics for glioma.IDH1 mutation occurs more frequently in grade Ⅱ and Ⅲ gliomas with R132 as the mutation site.