miR-216b-5p Promotes Ferroptosis in Glioblastoma Cells by Targeting NCOA3

Dong WANG; Bibo GAO; Huiying SUN; Denghui LENG; Xiaoping RAN; Wen LIN

doi:10.12259/j.issn.2095-610X.S20230805

Volume 44 Issue 8

Aug. 2023

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Dong WANG, Bibo GAO, Huiying SUN, Denghui LENG, Xiaoping RAN, Wen LIN. miR-216b-5p Promotes Ferroptosis in Glioblastoma Cells by Targeting NCOA3[J]. Journal of Kunming Medical University, 2023, 44(8): 44-52. doi: 10.12259/j.issn.2095-610X.S20230805

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Dong WANG, Bibo GAO, Huiying SUN, Denghui LENG, Xiaoping RAN, Wen LIN. miR-216b-5p Promotes Ferroptosis in Glioblastoma Cells by Targeting NCOA3[J]. Journal of Kunming Medical University, 2023, 44(8): 44-52. doi: 10.12259/j.issn.2095-610X.S20230805

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miR-216b-5p Promotes Ferroptosis in Glioblastoma Cells by Targeting NCOA3

doi: 10.12259/j.issn.2095-610X.S20230805

1.
Dept. of Neuromedical Center，Ziyang People’s Hospital of Sichuan Province，Ziyang Sichuan 641300
2.
Dept. of Neurosugery，First Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650032，China

Received Date: 2023-04-19
Available Online: 2023-09-01
Publish Date: 2023-08-30

Abstract

Abstract

Objective To investigate the effect of miR-216b-5p on ferroptosis in glioblastoma cells by targeting NCOA3, with a view to providing new targets for the clinical treatment of glioblastoma. Methods U251 cells were divided into DMSO-treated group, Erastin-treated group, Erastin + mimic NC group, Erastin + miR-216b-5p mimic group, Erastin + pcDNA 3.1 group, Erastin + pcDNA-NCOA3 group, pcDNA + miR-216b-5p mimic+ pcDNA-NCOA3 group. The expression of miR-216b-5p and NCOA3 and the expression of ferroptosis -related proteins PTGS2, NOX1, ACSL4, GPX4, FTH1 were detected by real-time fluorescence quantitative PCR assay and Western blot, and cell proliferation and apoptosis were detected by CCK-8 and flow cytometry, and MDA, Fe²⁺, glutamine, glutamic acid and α-ketoglutarate by kit. Results miR-216b-5p was highly expressed in human glioblastoma cell lines LN229 and U251, and the viability of Erastin-stimulated U25 cells increased and the apoptosis rate decreased. After transfection with miR-216b-5p mimics, MDA, Fe²⁺, glutamine, glutamic acid and α-ketoglutarate were all decreased significantly, and the expression of ferroptosis-related proteins PTGS2, NOX1, and ACSL4 increased significantly upon Erastin stimulation, while the protein amount of GPX4 and FTH1 decreased significant. 9 genes associated with ferroptosis in glioblastoma and directly targeted to miR-261b-5p were obtained, namely FOXO4, NCOA3, PARP8, PARP11, LIG3, MAPK9, TLR4, RB1, PTEN, miR-216b-5p, which directly bind to and negatively regulate NCOA3. Transfection with NCOA3 decreased cell viability, MDA, Fe²⁺, glutamine, glutamic acid, α-ketoglutarate levels, the protein expression of PTGS2, NOX1 and ACSL4 increased and that of GPX4 and FTH1 decreased; however, transfection of miR-216b-5p mimic reversed these results. Conclusion This study found that miR-216b-5p directly targets NCOA3 and regulates ferroptosis in glioblastoma cells through NCOA3, thereby promoting apoptosis. This study suggests new therapeutic targets for glioblastoma as well as new possibilities for subsequent research, in order to provide new ideas for the treatment of glioblastoma.
- Glioblastoma,
- miR-216b-5p,
- NCOA3,
- Ferroptosis

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