دورية أكاديمية

ALKBH5 is a prognostic factor and promotes the angiogenesis of glioblastoma

التفاصيل البيبلوغرافية
العنوان: ALKBH5 is a prognostic factor and promotes the angiogenesis of glioblastoma
المؤلفون: Fan, Yugeng, Yan, Dujuan, Ma, Lijun, Liu, Xiaoxi, Luo, Guoqiang, Hu, Yan, Kou, Xin
المساهمون: National Natural Science Foundation of Shaanxi Province
المصدر: Scientific Reports ; volume 14, issue 1 ; ISSN 2045-2322
بيانات النشر: Springer Science and Business Media LLC
سنة النشر: 2024
مصطلحات موضوعية: Multidisciplinary
الوصف: Despite numerous reports indicating the significant impact of RNA modification on malignant glioblastoma (GBM) cell behaviors such as proliferation, invasion and therapy efficacy, its specific involvement in glioblastoma (GBM) angiogenesis is remains unclear and is currently under investigation. In this study, we aimed to investigate the relevance between RNA modification regulators and GBM angiogenesis. Our study employed bioinformatic analyses, including Gene Set Enrichment Analysis (GSEA), differential expression analysis, and Kaplan–Meier survival analysis, to identify regulators of angiogenesis-associated RNA modification (RM). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied to identify the enrichment of angiogenesis associated signatures in ALKBH5-high expression GBMs. We also utilized Western blot to verify the upregulation of ALKBH5 in clinical GBM samples. By a series of in vitro and in vivo assays, including plasmid transfection, wound healing, transwell invasion test, tube formation, RT-qPCR, ELISA assays and xenograft mice model, we validated the angiogenesis regulation ability of ALKBH5 in GBM. The N6-methyladenosine (m6A) modification “erase” ALKBH5 emerged as a candidate regulator associated with angiogenesis, demonstrating elevated expression and robust prognostic predictive ability in GBM patients. We also revealed enrichment of vasculature development biological process in GBMs with high ALKBH5 expression. Subsequently, we validated the elevated the expression of ALKBH5 in clinical GBM and paired adjacent tissues through western blot. Additionally, we knocked down the expression of ALKBH5 using sh-RNAs in U87 GBM cells to access the angiogenesis induction ability in U87 cells. In vitro experiments, Human Umbilical Vein Endothelial Cells (HUVECs) were used to perform wound healing, transwell migration and tube formation analysis, results indicated that ALKBH5 knock-down of U87 cells could decrease the pro-angiogenesis ability of U87 GBM cells. ...
نوع الوثيقة: article in journal/newspaper
اللغة: English
DOI: 10.1038/s41598-024-51994-9
الإتاحة: https://doi.org/10.1038/s41598-024-51994-9Test
https://www.nature.com/articles/s41598-024-51994-9.pdfTest
https://www.nature.com/articles/s41598-024-51994-9Test
حقوق: https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test
رقم الانضمام: edsbas.B55B74B2
قاعدة البيانات: BASE