LncRNA-TIL1H mediates targeted regulation of the drug-resistant gene MDR1 and RAD21 to promote immune resistance and accelerate osteosarcoma progression

Abstract

BackgroundTargeted regulation of drug-resistant gene expression through lncRNA has emerged as a novel research direction for overcoming immune resistance in osteosarcoma. However, the specific effects and regulatory mechanisms of lncRNA-TIL1H on immune resistance in osteosarcoma remain unclear.ObjectiveTo explore the mechanism by which lncRNA-TIL1H targets the regulation of the drug-resistant genes MDR1 and RAD21.MethodsClinical samples including osteosarcoma tissues and adjacent tissues were collected for qPCR and WB analysis of lncRNA-TIL1H expression as well as MDR1 and RAD21. Acquisition of drug-resistant osteosarcoma cells by cisplatin treatment MG-63/R. The cells were divided into four groups: MG-63, MG-63/R, si-NC-MG-63/R, and si-TIL1H-MG-63/R group. Cell proliferation and colony formation, and migration and invasion were detected by CCK-8, Transwell and scratch assays. In addition, the effects on osteosarcoma after interfering with lncRNA-TIL1H were further explored by the animal experiments, including HE staining and immunohistochemistry.ResultsThe expression of lncRNA-TIL1H and the drug-resistant genes MDR1 and RAD21 significantly increased in osteosarcoma. si-TIL1H effectively inhibited cell proliferation, invasion, migration and decreased the expression of drug-resistant genes in MG-63/R. Finally, the animal experiments revealed that si-lncRNA-TIL1H inhibited tumor proliferation.ConclusionThe expression of lncRNA-TIL1H in MG-63/R promotes the upregulation of drug-resistant genes MDR1 and RAD21, leading to the occurrence of immune resistance and accelerating osteosarcoma progression.

Keywords: MDR1; Osteosarcoma; RAD21; drug-resistant; immune resistance; lncRNA-TIL1H.