Long Noncoding RNA RP11-732M18.3 Promotes Glioma Angiogenesis by Upregulating VEGFA

Abstract

Gliomas are the most aggressive and common type of malignant brain tumor, with limited treatment options and a dismal prognosis. Angiogenesis, a hallmarks of cancer, is one of two critical events in the progression of gliomas. Accumulating evidence has demonstrated that in glioma dysregulated molecules like long noncoding RNAs (lncRNAs), are closely linked to tumorigenesis and prognosis. However, the effects of and mechanisms of action of lncRNAs during tumor angiogenesis are poorly understood. The effect of lncRNA RP11-732M18.3 on angiogenesis was elucidated through an intracranial orthotopic glioma model, immunohistochemistry, and an in vitro angiogenesis assay. Co-culture experiments and cell migration assays were performed to investigate the function of lncRNA RP11-732M18.3 in vitro. lncRNA RP11-732M18.3 increased CD31+ microvessel density, and overexpression of lncRNA RP11-732M18.3 resulted in poor mouse survival. lncRNA RP11-732M18.3 promoted endothelial cell migration and tube formation. Nomogram and Kaplan-Meier survival analyses indicated that higher VEGFA is correlated with a poor prognosis. Mechanistically, lncRNA RP11-732M18.3 promotes angiogenesis by increasing the nuclear level of EP300 and facilitating the transcription and secretion of VEGFA. Our study contributes to the latest understanding of glioma angiogenesis and prognosis. lncRNA RP11-732M18.3 may be a potential treatment target in glioma.

Regulation of VEGF-A expression and VEGF-A-targeted therapy in malignant tumors

“…Circ-RPL15 up-regulates VEGF-A by competitively binding miR-146b-3p, thereby triggering proliferation and migration potential of glioma (Wang et al 2020a , b ). Except as ceRNA, LncRNA RP11-732M18.3 promotes EP300 into the nucleus to enhance transcription and secretion of VEGF-A, and thus promote angiogenesis in glioma (Kang et al 2022 ). TPT1-AS1 regulates angiogenesis in colon cancer by regulating expression and stability of VEGF-A mRNA through NF90 (Zhang et al 2020a , b , c , d ).…”

A novel inflammation-related lncRNAs prognostic signature identifies LINC00346 in promoting proliferation, migration, and immune infiltration of glioma

“…Bioinformatics analysis found that lncRNA expression patterns in clinical glioma specimens correlated with histological differentiation and malignancy grade, which may have remarkable clinical impacts for glioma sub-classification, diagnosis, and prognostication ( 20 ). Other studies found that RP11-732M18.3 was highly overexpressed in glioma cells, which not only promote glioma angiogenesis by accelerating the transcription and secretion of VEGFA but also facilitate glioma growth through accelerating p21 degradation ( 21 , 22 ). More recently, a risk model of constructed from eleven inflammation-related lncRNAs was reported as a potential prognostic biomarker for patients with lower-grade gliomas ( 23 ).…”