Glioblastoma (GBM) is a deadly and incurable brain tumor. Although microRNAs (miRNAs) play critical roles in regulating the cancer cell phenotype, the underlying mechanisms of how they regulate tumorigenesis are incompletely understood. We found that miR-1 is expressed at relatively low levels in brain cancer patients, especially GBM. Ectopic miR-1 expression in GBM cells inhibited proliferation and migration, increased sensitivity to apoptosis induced by the DNA alkylating agent temozolomide in vitro, and inhibited GBM tumorigenesis in vivo. Expression of miR-1 in GBM cell lines directly targets fibronectin. High fibronectin expression in GBM correlates with poor patient survival and fibronectin expression is inversely correlated with miR-1 expression. Knockout of fibronectin expression in GBM cell lines inhibited proliferation and migration, increased sensitivity to apoptosis induced by temozolomide in vitro, and markedly suppressed GBM tumor growth and promoted animal survival. In contrast, restoring fibronectin levels in GBM cells ectopically expressing miR-1 increased tumorigenicity and decreased animal survival. Therefore, these results confirm that miR-1 has tumor suppressive activity in GBM by targeting fibronectin, and that the miR-1/fibronectin pathway may be a potential drug target in this devastating cancer.
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http://dx.doi.org/10.1016/j.canlet.2019.08.021 | DOI Listing |
Sci Rep
January 2025
Biochemistry Department, Biotechnology Research Institute, National Research Centre, Dokki, Giza, Egypt.
Glioblastoma multiforme (GBM) is the most prevalent, treatment-resistant, and fatal form of brain malignancy. It is characterized by genetic heterogeneity, and an infiltrative nature, and GBM treatment is highly challenging. Despite multimodal therapies, clinicians lack efficient prognostic and predictive markers.
View Article and Find Full Text PDFJ Mol Neurosci
January 2025
Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China.
Hemorrhagic stroke is a known complication of glioma, yet the underlying mechanisms remain poorly understood. This study aims to investigate key biomarkers of glioma-related hemorrhage to provide insights into glioma molecular therapies. Data were obtained from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases to analyze differentially expressed genes (DEGs) in glioma by contrasting glioblastoma (GBM) with low-grade gliomas (LGGs).
View Article and Find Full Text PDFSci China Life Sci
January 2025
Nanhu Laboratory, National Center of Biomedical Analysis, Beijing, 100850, China.
The infiltration of glioblastoma multiforme (GBM) is predominantly characterized by diffuse spread, contributing significantly to therapy resistance and recurrence of GBM. In this study, we reveal that microtubule deacetylation, mediated through the downregulation of fibronectin type III and SPRY domain-containing 1 (FSD1), plays a pivotal role in promoting GBM diffuse infiltration. FSD1 directly interacts with histone deacetylase 6 (HDAC6) at its second catalytic domain, thereby impeding its deacetylase activity on α-tubulin and preventing microtubule deacetylation and depolymerization.
View Article and Find Full Text PDFCell Death Dis
January 2025
Division of Hematology and Oncology, Department of Pediatrics, Penn State College of Medicine, Hershey, PA, USA.
The association of necrosis in tumors with poor prognosis implies a potential tumor-promoting role. However, the mechanisms underlying cell death in this context and how damaged tissue contributes to tumor progression remain unclear. Here, we identified p38 mitogen-activated protein kinases (p38 MAPK, a.
View Article and Find Full Text PDFDiscov Oncol
January 2025
Department of Medical Imaging, Shenzhen Longhua District Key Laboratory of Neuroimaging, Shenzhen Longhua District Central Hospital, Shenzhen, 518110, China.
Background: Glioblastoma multiforme (GBM) is a highly aggressive brain cancer with poor prognosis and limited treatment options. Despite advances in understanding its molecular mechanisms, effective therapeutic strategies remain elusive due to the tumor's genetic complexity and heterogeneity.
Methods: This study employed a comprehensive analysis approach integrating 113 machine learning algorithms with Mendelian Randomization (MR) analysis to investigate the molecular underpinnings of GBM.
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