Silencing of Long Noncoding RNA HLA Complex P5 (HCP5) Suppresses Glioma Progression through the HCP5-miR-205-Vascular Endothelial Growth Factor A Feedback Loop

Abstract

Long noncoding RNA (lncRNA) HLA complex P5 (HCP5) is correlated with multiple diseases, especially cancers. However, it remains to be further studied whether HCP5 is involved in the malignant behaviors of gliomas. This study is aimed at investigating the role and regulation mechanisms of HCP5 in gliomas. HCP5 expression in glioma tumor tissues and its association with glioma patients' survival were analyzed based on RNA-sequencing data. The expression of HCP5 was also examined in glioma cells. Then, HCP5 was downregulated in U251 cells and/or primary glioblastoma cells to explore its effects on cell proliferation and migration. The influence of HCP5 downregulation on tumor growth was confirmed in xenograft mice. About the mechanism, we investigated whether HCP5 functioned via interacting with microRNA- (miR-) 205 and regulating vascular endothelial growth factor A (VEGF-A) expression in gliomas. Results showed that HCP5 upregulation was found in glioma tissues and cell lines. Patients with high HCP5 expression showed lower survival probability and shorter survival time. HCP5 downregulation inhibited cell proliferation and migration and mitigated tumor growth. miR-205 was downregulated in glioma cells. Knockdown of HCP5 led to miR-205 upregulation and VEGF-A downregulation. miR-205 overexpression exhibited the similar effects as HCP5 downregulation on cell viability and proliferation. And VEGF-A overexpression could reverse the effects of HCP5 downregulation on cell viability and proliferation, as well as tumor growth. In conclusion, HCP5 silencing suppressed glioma progression through the HCP5-miR-205-VEGF-A feedback loop.