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IDH1 mutation produces R-2-hydroxyglutarate (R-2HG) and induces mir-182-5p expression to regulate cell cycle and tumor formation in glioma.
Zhao, Haiting; Meng, Li; Du, Peng; Liao, Xinbin; Mo, Xin; Gong, Mengqi; Chen, Jiaxin; Liao, Yiwei.
Afiliação
  • Zhao H; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, P.R. China.
  • Meng L; Department of Neurology, Xiangya Hospital, The Central South University (CSU), Changsha, 410008, P.R. China.
  • Du P; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, P.R. China.
  • Liao X; Department of Radiology, Xiangya Hospital, Central South University (CSU), Changsha, 410008, P.R. China.
  • Mo X; Department of Neurosurgery, The Second Affiliated Hospital, Xinjiang Medical University, Urumqi, 830063, PR China.
  • Gong M; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, P.R. China.
  • Chen J; Department of Neurosurgery, Xiangya Hospital, Central South University (CSU), Changsha, 410008, P.R. China.
  • Liao Y; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, P.R. China.
Biol Res ; 57(1): 30, 2024 May 17.
Article em En | MEDLINE | ID: mdl-38760850
ABSTRACT

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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / MicroRNAs / Glioma / Isocitrato Desidrogenase Limite: Animals / Humans Idioma: En Revista: Biol Res Assunto da revista: BIOLOGIA Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / MicroRNAs / Glioma / Isocitrato Desidrogenase Limite: Animals / Humans Idioma: En Revista: Biol Res Assunto da revista: BIOLOGIA Ano de publicação: 2024 Tipo de documento: Article