Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malignant glioma is the most common type of primary brain tumor in adults, characterized by rapid tumor growth and infiltration of tumor cells throughout the brain. Alterations in the activity of the 26S proteasome have been associated with malignant glioma cells, although the specific defects have not been identified. Recently, microRNA-326 (miR-326) was shown to play an important role in glioblastoma and breast cancer, but the underlying molecular mechanisms remain unclear. In the present study, the human Nin one binding protein (NOB1) was identified as a direct target of miR-326 and a potential oncogene in human glioma. Similar to NOB1 silencing by shRNA, overexpression of miR-326 in human glioma cell lines (A172 and U373) caused cell cycle arrest at the G1 phase, delayed cell proliferation and enhanced apoptosis. MiR-326 inhibited colony formation in soft agar and decreased growth of a xenograft tumor model, suggesting that miR-326 and NOB1 are required for tumorigenesis in vitro and in vivo. Furthermore, these processes were shown to involve the MAPK pathway. NOB1 overexpression in human glioma samples was detected by Affymetrix array analysis, and NOB1 mRNA and protein levels were shown to be increased in high-grade glioma compared to low-grade glioma and normal brain tissue. Furthermore, high levels of NOB1 were associated with unfavorable prognosis of glioma patients. Taken together, these results indicate that miR-326 and NOB1 may play an important role in the development of glioma.
...
PMID:MicroRNA-326 functions as a tumor suppressor in glioma by targeting the Nin one binding protein (NOB1). 2386 22

In recent years, changes in microRNA (miRNA) expression have been detected in almost all human cancer types, including glioblastoma (GBM). Dysregulation of miRNAs may play tumor-suppressing or oncogenic roles in the initiation and progression of GBM, and may be involved in the regulation of multiple pathological behaviors. Therefore, identifying the clinical value and functional role of GBM-related miRNAs may provide effective therapeutic targets for the treatment of patients with this fatal malignancy. Dysregulation of miR-744 has been identified in several human cancer types. However, to the best of our knowledge, little is known concerning the expression pattern and biological roles of miR-744 in GBM. In this study, we found that miR-744 was significantly downregulated in GBM tissues and cell lines. Decreased miR-744 expression was significantly correlated with the Karnofsky Performance Scale (KPS) and World Health Organization (WHO) grade in GBM patients. miR-744 upregulation inhibited the proliferation, colony formation, migration, and invasion, in addition to inducing apoptosis of GBM cells in vitro. Inhibition of miR-744 had the opposite effect on these behaviors in GBM cells. Additionally, miR-744 attenuated the tumor growth of GBM cells in vivo. Furthermore, NIN1/RPN12 binding protein1 homolog (NOB1) was identified as a direct target gene of miR-744 in GBM cells. NOB1 was confirmed to be upregulated in GBM tissues, and this was inversely correlated with upregulation of miR-744 expression. Moreover, NOB1 knockdown exhibited similar inhibitory effects as miR-744 overexpression in GBM cells. Notably, recovered NOB1 expression counteracted the tumor-suppressing roles of miR-744 in the malignant phenotypes of GBM cells. Taken together, these results demonstrate that miR-744 directly targets NOB1 to inhibit the aggressive behaviors of GBM cells. Hence, the miR-744/NOB1 axis may be useful in the identification of novel therapies for GBM patients.
 ...
PMID:microRNA-744 is downregulated in glioblastoma and inhibits the aggressive behaviors by directly targeting NOB1. 3055 41