The prognostic significance and immune correlation of SLC10A3 in low-grade gliomas revealed by bioinformatic analysis and multiple immunohistochemistry.

PURPOSE: Despite the fact that genetic risk factors contribute to low-grade gliomas (LGGs), the role of critical genes as prognostic and theraputic biomarkers is quite limited. This study is designed to comprehensively investigate the prognostic role and predictive ability of solute carrier family 10 member 3 (SLC10A3) for immunotherapy in LGGs. METHODS: We analyzed the prognostic value of SLC10A3 from multiple datasets of LGG patients, and explored its immune correlation via multiple algorithms. Finally, we independently confirmed the clinical significance and its immune correlation using the multiplex staining assay of LGG samples on the tissue microarray. RESULTS: SLC10A3 mRNA was up-regulated in LGGs compared with normal brain tissues, and correlated with tumor grade, histological type, IDH wide type and non-codel 1p19q. Up-regulation of SLC10A3 transcription was remarkably associated with shortened overall survival time compared with down-regulation in TCGA, CGGA and Rembrandt datasets, and SLC10A3 exhibited good predictive ability for survival outcomes among LGGs. Correlation analyses showed that SLC10A3 mRNA expression correlates well with the six immune check points and immune cells. When the expression and immune correlation of SLC10A3 at the translational level were verified via multiplex immunohistochemistry, expression of SLC10A3 protein was higher in LGG compared with normal tissues, and expression of SLC10A3 protein was correlated well with macrophage, CD4 + T cell and B cell. CONCLUSIONS: Up-regulation of SLC10A3 mRNA is statistically associated with adverse survival outcomes and immune infiltration among LGGs. SLC10A3 might be a reliable survival predictor and a promising immunotherapy target for LGG patients.

circ_CHFR regulates ox-LDL-mediated cell proliferation, apoptosis, and EndoMT by miR-15a-5p/EGFR axis in human brain microvessel endothelial cells.

Oxidized low-density lipoprotein (ox-LDL) is a significant risk factor for various brain vascular diseases. Circular RNA (circRNA) is involved in the pathogenesis of brain vascular diseases. This study revealed the roles of circ_CHFR in ox-LDL-mediated cell proliferation, apoptosis, and endothelial-to-mesenchymal transition (EndoMT). Our results showed that circ_CHFR and EGFR expressions were dramatically upregulated, while miR-15a-5p expression was downregulated in ox-LDL-induced human brain microvessel endothelial cells (HBMECs) relative to control groups. circ_CHFR knockdown hindered the effects of ox-LDL exposure on cell proliferation, cell cycle, apoptosis, and EndoMT in HBMECs, whereas these impacts were abolished by miR-15a-5p inhibitor. In addition, circ_CHFR functioned as a sponge of miR-15a-5p and miR-15a-5p bound to EGFR. Thus, we concluded that circ_CHFR silencing hindered ox-LDL-mediated cell proliferation, apoptosis, and EndoMT by downregulating EGFR expression through sponging miR-15a-5p in HBMECs. Our findings provide a new mechanism for studying circRNA-directed therapy in ox-LDL-induced human brain vascular diseases.