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EZH2 Promotes Glioma Cell Proliferation, Invasion, and Migration via Mir-142-3p/KCNQ1OT1/HMGB3 Axis

Running Title: EZH2 Promotes Glioma cell Malignant Behaviors

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Abstract

This study investigates the role and molecular mechanism of EZH2 in glioma cell proliferation, invasion, and migration. EZH2, miR-142-3p, lncRNA KCNQ1OT1, LIN28B, and HMGB3 expressions in glioma tissues and cells were determined using qRT-PCR or Western blot, followed by CCK-8 assay detection of cell viability, Transwell detection of invasion and migration, ChIP analysis of the enrichment of EZH2 and H3K27me3 on miR-142-3p promoter, dual-luciferase reporter assay and RIP validation of the binding of miR-142-3p-KCNQ1OT1 and KCNQ1OT1-LIN28B, and actinomycin D detection of KCNQ1OT1 and HMGB3 mRNA stability. A nude mouse xenograft model and a lung metastasis model were established. EZH2, KCNQ1OT1, LIN28B, and HMGB3 were highly expressed while miR-142-3p was poorly expressed in gliomas. EZH2 silencing restrained glioma cell proliferation, invasion, and migration. EZH2 repressed miR-142-3p expression by elevating the H3K27me3 level. miR-142-3p targeted KCNQ1OT1 expression, and KCNQ1OT1 bound to LIN28B to stabilize HMGB3 mRNA, thereby promoting its protein expression. EZH2 silencing depressed tumor growth and metastasis in nude mice via the miR-142-3p/KCNQ1OT1/HMGB3 axis. In conclusion, EZH2 curbed miR-142-3p expression, thereby relieving the inhibition of KCNQ1OT1 expression by miR-142-3p, enhancing the binding of KCNQ1OT1 to LIN28B, elevating HMGB3 expression, and ultimately accelerating glioma cell proliferation, invasion, and migration.

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Acknowledgements

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Funding

This study was not supported by any sponsor or funder.

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Authors and Affiliations

  1. Department of Neurosurgery, Beijing Fengtai You’anmen Hospital, Beijing, 100069, China

    Yiming Zhang

  2. Epilepsy Center, Beijing Fengtai You’anmen Hospital, Beijing, 100069, China

    Yong Yu

  3. Department of Neurosurgery, PLA Rocket Force Characteristic Medical Center, No. 16, Xin Jie Kou Wai Street, Beijing, 100088, China

    Lei Yuan

  4. Department of Neurosurgery, He Bei Hua Ao Hospital, No. 11, the Changcheng West Street, Zhangjiakou, 075000, Hebei Province, China

    Baozhong Zhang

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Contributions

Yiming Zhang: Conceptualization, Data curation, Investigation, Methodology, Writing – original draft, Writing – review & editing; Yong Yu: Data curation, Visualization; Lei Yuan: Investigation, Validation; Baozhong Zhang: Conceptualization, Formal Analysis, Methodology, Supervision.

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Correspondence to Lei Yuan or Baozhong Zhang.

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Ethical Approval

Tthe study procedure was approved by the Ethics Committee of Beijing Fengtai You’anmen Hospital (Approval number: 2022-08-053). All animal experiment schemes were approved by the Animal Ethics Committee of Beijing Fengtai You’anmen Hospital (Approval number: 2023-03-032) and implemented based on the Guide for the Care and Use of Laboratory Animals [23].

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Zhang, Y., Yu, Y., Yuan, L. et al. EZH2 Promotes Glioma Cell Proliferation, Invasion, and Migration via Mir-142-3p/KCNQ1OT1/HMGB3 Axis. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-04080-0

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