Aberrant ceRNA-mediated regulation of KNG1 contributes to glioblastoma-induced angiogenesis

Abstract

Glioblastoma is a highly vascularized brain tumor that causes high mortality. Kininogen-1 (KNG1) has demonstrated both tumor suppressor and antiangiogenesis properties in gliobastoma cells. We analyzed the microarray and proteomic profiles of tumor tissues from glioblastoma patients (N = 180), and identified potential RNA regulators of the KNG1. Validation experiments in U87 glioblastoma cells showed that the regulation of KNG1 by CTU1, KIAA1274, and RAX was mediated by miR-138. The siRNA-mediated knockdown of CTU1, KIAA1274, or RAX in U87 cells and immortalized human endothelial cells (iHECs) significantly reduced KNG1 expression (P < 0.05 for all), which resulted in the upregulation of oncogenic EGFR signaling in both cell lines, and stimulated angiogenic processes in cultured iHECs and zebrafish and mouse xenograft models of glioblastoma-induced angiogenesis. Angiogenic transduction of iHECs occurred via the uptake of U87-derived exosomes enriched in miR-138, with the siRNA-mediated knockdown of KNG1, CTU1, KIAA1274, or RAX increasing the level of miR-138 enrichment to varying extents and enhancing the angiogenic effects of the U87-derived exosomes on iHECs. The competing endogenous RNA network of KNG1 represents potential targets for the development of novel therapeutic strategies for glioblastoma.

Proteomic Alterations in Multiple Myeloma: A Comprehensive Study Using Bone Marrow Interstitial Fluid and Serum Samples

“…Bradykinin plays an important role in several physiological activities such as antimicrobial, smooth muscle contraction and release of inflammatory mediators like prostaglandins (65). Moreover, bradykinin is also known to interact with EGFR and stimulate downstream signaling pathways to enhance cell invasion as well as promote angiogenesis through elevated VEGF expression in glioma (66,67). Furthermore, higher expression of kininogen 1 is recently reported as a serum biomarker of advanced colorectal adenoma, colorectal cancer and prognostic marker of oral cancer (68,69).…”

Investigation of Candidate Genes and Mechanism Associated with Immune Cell during the Progression of Glioblastoma based on Bioinformatics

“…Meanwhile, some immune-related lncRNAs such as RP11-161H23.5 contributes to the prognosis prediction of GBM via certain lncRNA-miRNA interactions [46]. Actually, the lncRNA-miRNA-mRNA regulation take part in the malignant progression of GBM disease identi cation and functional characterization [47]. A previous differential correlation analysis of GBM reveals that immune ceRNA interactions can be used to predict the patient survival [48].…”

Transcriptome profiling analysis of sex-based differentially expressed mRNAs and lncRNAs in the brains of mature zebrafish (Danio rerio)

“…We have found that some genes have not been thoroughly studied in zebrafish, but have been identified to be important in human brain neural networks and diseases. For example, kng1 (kininogen 1) demonstrated tumor suppression and anti-angiogenic properties in glioblastoma [30]. Aldh1l1 (aldehyde dehydrogenase 1 family member L1) was also identified as a new astrocyte-specific marker in the brain [31].…”