Figure 3

Schematic diagram showing the multi-regulation loops of LRRC4/NGL-2, miRNAs, TFs and target genes in glioma. LRRC4/NGL-2-AP-2-miR-182- LRRC4/NGL-2 loop: LRRC4/NGL-2 is a target of miR182; meanwhile, the overexpression of LRRC4/NGL-2 downregulated the expression of miR182. The transcription of miR-182 was induced by AP-2; meanwhile, miR-182 can inhibit the expression of LRRC4/NGL-2, and LRRC4/NGL-2 can inhibit the expression of AP-2 though negatively regulating the ERK/MAPK and PI-3K/AKT signaling pathways. The LRRC4/NGL-2-AP-2-miR-182- LRRC4/NGL-2 loop was formed among LRRC4/NGL-2, miR-182 and AP-2. LRRC4/NGL-2-miR-185-DNMT1-LRRC4/NGL-2 loop: The overexpression of LRRC4/NGL-2 could increase the expression of miR-185, while miR-185 could regulate global methylation by targeting DNMT1 and increasing the expression of LRRC4/NGL-2. LRRC4/NGL-2-SP1-DNMT1-LRRC4/NGL-2 loop: DNMT1 was positively regulated by SP1, and it could increase the expression of LRRC4/NGL-2, while LRRC4/NGL-2 could also inhibit SP1 by negatively regulating the ERK/MAPK and PI-3K/AKT signal pathway.