MicroRNA192-5p demethylation inhibits glucose metabolism and angiogenesis in non-small cell lung cancer by targeting EREG/PI3K/AKT

Abstract Background MicroRNA192-5p (miR-192-5p) regulates glucose metabolism to alter cancer metabolism. However, the role and molecular mechanism of miR-192-5p on glucose metabolism proteins in non-small cell lung cancer (NSCLC) are still unclear. The purpose is to investigate the effects of miR-192-5p and miR-192-5p demethylation on glucose metabolism-related proteins and angiogenesis, as well as molecular mechanisms in NSCLC. Methods H&E staining was used to detect tissue morphology. IHC and WB were used to measure protein expression. qRT-PCR was used to measure the miR-192-5p level. CCK-8 was used to test cell proliferation. Wound healing and tube formation were used to measure cell migration and angiogenesis. Dual luciferase was used to detect the interaction between miR-192-5p and target genes. Results In vivo, the expression of glucose metabolism-related proteins (GLUT-1, HKII, PFKFB3, and LDH) increased in NSCLC, and the level of miR-192-5p decreased. In vitro, overexpression of miR-192-5p or miR-192-5p demethylation inhibited the expression of glucose metabolism-related proteins in A549 cells and the proliferation, migration, and angiogenesis of HUVECs. Mechanistically, miR-192-5p could bind to EREG, reducing the activation of the glucose metabolism regulation pathway PI3K/AKT. DNA demethylation promoted the expression of miR-192-5p and regulated its function. Conclusion MiR-192-5p and miR-192-5p demethylation could regulate glucose metabolism and angiogenesis in NSCLC through EREG/PI3K/AKT, providing a new target for targeting glucose metabolism in NSCLC and improving prognosis.