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)

How necrotic areas develop in tumors is incompletely understood but can impact progression. Recent findings suggest that the formation of vascular microthrombi contributes to tumor necrosis, prompting investigation of coagulation cascades. Here, we report that loss of tumor suppressor P14ARF can contribute to activating the clotting cascade in glioblastoma. P14ARF transcriptionally upregulated TFPI2, a Kunitz-type serine protease in the tissue factor pathway that inhibits the initiation of thrombosis reactions. P14ARF activation in tumor cells delayed their ability to activate plasma clotting. Mechanistically, P14ARF activated the TFPI2 promoter in a p53-independent manner that relied upon c-JUN, SP1, and JNK activity. Taken together, our results identify the critical signaling pathways activated by P14ARF to prevent vascular microthrombosis triggered by glioma cells. Stimulation of this pathway might be used as a therapeutic strategy to reduce aggressive phenotypes associated with necrotic tumors, including glioblastoma.
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PMID:P14ARF suppresses tumor-induced thrombosis by regulating the tissue factor pathway. 2439 74

Long non-coding RNAs (LncRNAs) have attracted increasing attention for their important regulation functions in a wide range of malignancies. AGAP2-AS1 was demonstrated as an oncogene in several cancers, including glioblastoma (GBM). However, the biological mechanisms of AGAP2-AS1 in GBM progression are still unclear. Herein, we found that AGAP2-AS1 expression was up-regulated in GBM tissues and cells. High AGAP2-AS1 expression may predict a poor prognosis in GBM patients. Functionally, silencing of AGAP2-AS1 suppressed proliferation and invasion, while enhanced apoptosis in GBM cells. Overexpression of AGAP2-AS1 promoted cell proliferation and invasion. Mechanically, AGAP2-AS1 could interact with EZH2 and LSD1, recruiting them to TFPI2 promoter region to inhibit its transcription. Moreover, TFPI2 overexpression decreased proliferation and invasion, and facilitated apoptosis in GBM cells. Furthermore, the tumor-suppressive effects mediated by AGAP2-AS1 knockdown were greatly reversed following down-regulation of TFPI2. Also, suppression of AGAP2-AS1 impaired tumor growth of GBM in vivo. In summary, AGAP2-AS1 exerts oncogenic functions in GBM by epigenetically silencing TFPI2 expression through binding to EZH2 and LSD1, illuminating a novel mechanism of AGAP2-AS1 in GBM development and furnishing a prospective therapeutic method to combat GBM.
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PMID:Long non-coding RNA AGAP2-AS1 exerts oncogenic properties in glioblastoma by epigenetically silencing TFPI2 through EZH2 and LSD1. 3118 79