NUP37 promotes the proliferation and invasion of glioma cells through DNMT1-mediated methylation

Abstract

Abstract Purpose The objective of this study was to determine whether nucleoporin 37 (NUP37) could control the proliferation and invasion of glioma cells through DNA methyltransferase 1 (DNMT1), thus contributing to the onset and progression of glioma. Methods TCGA and GTEx public databases were employed to examine the expression of NUP37 and DNMT1 in glioma. The correlation between NUP37 and DNMT1 expression levels and clinical features, such as prognosis, World Health Organization (WHO), and histopathological types of glioma patients, was analyzed based on the TCGA database. qRT-PCR and Western blotting analysis were used to detect the expression levels of NUP37 and DNMT1 in glioma tissues, cell lines, and post-lentivirus transfection cells. Assays, such as MTT assay, CCK-8 assay, Transwell assay, flow cytometry, scratch test, and cell counting assay, were employed to identify the regulatory effects of NUP37 depletion on the proliferation, apoptosis, invasion, and cell cycle of glioma cells. Transcriptome sequencing combined with proteomic was utilized to examine the changes in genes, proteins, and signaling pathways post-NUP37 knockdown in glioma cells to uncover the effects of changes in target molecules upstream and downstream of NUP37 on glioma cell biological functions. The co-immunoprecipitation (Co-IP) assay was used to investigate the interaction between NUP37 and DNMT1. Lastly, the rescue assay was used to assess whether NUP37 regulated the proliferation and invasion of glioma cells via DNMT1. Results Bioinformatic analysis revealed that NUP37 and DNMT1 were overexpressed in glioma and closely correlated with clinical features, such as prognosis and WHO grades of glioma. The expression of NUP37 and DNMT1 in glioma tissues was significantly higher than in normal brain tissue respectively. NUP37 depletion could suppress the proliferation and invasion of U87 and U251 glioma cells, induce apoptosis, and cause cell cycle arrest. Co-IP experiments indicated that NUP37 could bind DNMT1. Transcriptome sequencing combined with proteomic sequencing showed a decrease in the expression of certain genes, proteins (including DNMT1), and some signaling pathways following NUP37 depletion in glioma cells. Western blotting analysis indicated a decrease in the expression of DNMT1 at the protein level upon NUP37 depletion. The recovery experiment demonstrated that DNMT1 overexpression could restore the proliferation and invasion capacity of glioma cells and reduce the apoptosis rate of these cells. Conclusion These findings suggested that high expression of NUP37 regulated the proliferation and invasion of glioma cells by binding DNMT1.