Hsa-miR-503-5p regulates CTDSPL to accelerate cisplatin resistance and angiogenesis of lung adenocarcinoma cells.

Abstract

The study aimed to assess the role of hsa-miR-503-5p in cisplatin resistance and angiogenesis in LUAD and its underlying mechanisms. Hsa-miR-503-5p expression in LUAD and the target gene downstream of hsa-miR-503-5p was predicted by bioinformatics analysis. Binding relationship between the two genes was verified by dual-luciferase reporter assay. qRT-PCR was conducted for detecting gene expression in cells, CCK-8 for IC50 value, angiogenesis assay for human umbilical vein endothelial cell (HUVEC) angiogenic ability, flow cytometry for apoptosis ability, transwell assay for migration ability, and western blot for detecting the protein expression of vascular endothelial growth factor receptor 1 (VEGFR1), VEGFR2, and CTD small phosphatase like (CTDSPL). The results showed that hsa-miR-503-5p showed high expression, while its target gene CTDSPL presented decreased expression in LUAD. Hsa-miR-503-5p also had high expression in cisplatin-resistant LUAD cells. Knockdown of hsa-miR-503-5p resensitized LUAD cells to cisplatin, inhibited angiogenesis of drug-resistant cells, and reduced the protein expression of VEGFR1, VEGFR2, and EMT-related targets in cisplatin-resistant LUAD cells, but promoted the apoptosis ability. Hsa-miR-503-5p bound to CTDSPL gene and promoted cisplatin resistance and malignant progression of LUAD cells by negatively regulating CTDSPL. Our results revealed that hsa-miR-503-5p and CTDSPL may be novel targets for overcoming cisplatin resistance in LUAD.