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

• DOI: 10.3892/ijmm.2021.5071
• Publication Date: 2021-12-08T12:51:17Z
• Authors: Jing Zhang; Yunna Yang; Yipeng Dong; Cang Liu
• Keywords: 0303 health sciences; Epithelial-Mesenchymal Transition; Intracellular Signaling Peptides and Proteins; PTEN Phosphohydrolase; Cell Cycle Proteins; Articles; Glioma; Up-Regulation; 3. Good health; Gene Expression Regulation, Neoplastic; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Cell Movement; Cell Line, Tumor; Disease Progression; Humans; Neoplasm Invasiveness; Gene Silencing; Promoter Regions, Genetic; Proto-Oncogene Proteins c-akt; Cell Proliferation; Protein Binding; Signal Transduction; Transcription Factors

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