Microrchidia family CW‑type zinc finger 2 promotes the proliferation, invasion, migration and epithelial‑mesenchymal transition of glioma by regulating PTEN/PI3K/AKT signaling via binding to N‑myc downstream regulated gene 1 promoter

Zhang,Jing; Yang,Yunna; Dong,Yipeng; Liu,Cang

doi:10.3892/ijmm.2021.5071

Microrchidia family CW‑type zinc finger 2 promotes the proliferation, invasion, migration and epithelial‑mesenchymal transition of glioma by regulating PTEN/PI3K/AKT signaling via binding to N‑myc downstream regulated gene 1 promoter

Authors:
- Jing Zhang
- Yunna Yang
- Yipeng Dong
- Cang Liu
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Affiliations: Department of Neurosurgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China, Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100053, P.R. China
Published online on: December 8, 2021 https://doi.org/10.3892/ijmm.2021.5071
Article Number: 16
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Glioma is a common malignant tumor of the central nervous system with high incidence and mortality. The present study aimed to investigate the role of Microrchidia family CW‑type zinc finger 2 (MORC2) in the development of glioma. Firstly, MORC2 expression was detected in several glioma cell lines (U251, SHG44, LN229 and T98G). Following MORC2 silencing, cell proliferation was evaluated using the Cell Counting Kit‑8 assay and the expression of proliferation‑related proteins was assessed via immunofluorescence staining or western blotting. Cell invasion and migration were assessed using transwell and wound healing assays, respectively. Western blotting and immunofluorescence staining were employed to determine the expression of epithelial‑mesenchymal transition (EMT)‑associated proteins. The protein expression of N‑myc downstream regulated gene 1 (NDRG1) and PTEN/PI3K/AKT signaling was determined with western blot analysis. Then, the luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were employed to evaluate the binding between MORC2 and NDRG1 promoter. Subsequently, cellular functional experiments were performed to assess the effects of NDRG1 on the progression of glioma after NDRG1 and MORC2 overexpression. In addition, tumor‑bearing experiments were conducted using a U251 tumor‑bearing nude mice model to detect tumor growth. The expression of proliferation (proliferating cell nuclear antigen, cyclin‑dependent kinase 2 and cyclin E1), migration [matrix metalloproteinase (MMP)2 and MMP9], EMT (E‑cadherin, N‑cadherin and Vimentin) and PTEN/PI3K/AKT signaling proteins in tumor tissues was examined with immunohistochemistry assay or western blotting. Results revealed that MORC2 was notably unregulated in glioma cells compared with the normal human astrocyte. Loss‑function of MORC2 inhibited the proliferation, invasion, migration and EMT of glioma cells. Importantly, MORC2 silencing upregulated NDRG1 expression and inactivated PTEN/PI3K/AKT signaling. Additionally, the luciferase reporter‑ and ChIP assays confirmed that MORC2 could bind to the NDRG1 promoter. NDRG1 upregulation suppressed the progression of glioma and these effects were partially reversed by MORC2 overexpression. Results of tumor‑bearing experiments suggested that gain‑function of NDRG1 inhibited tumor growth and downregulated the expression of proliferation, migration and EMT‑related proteins in tumorous tissue in U251 tumor‑bearing mice, which was partially counteracted after MORC2 overexpression. In addition, MORC2 overexpression abrogated the inhibitory effect of NDRG1 on PTEN/PI3K/AKT signaling. In summary, MORC2 promoted the progression of glioma by inactivation of PTEN/PI3K/AKT signaling via binding to NDRG1 promoter, providing a novel and potent target for the treatment of glioma.

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