KCNQ1OT1 Promotes Cisplatin Resistance Of Osterosarcoma Cancer Cells Through MiR-335-5p/β-catenin Axis

With the advancement of medicine,the treatment of osteosarcoma(Osteosarcoma,OS)has been gradually changed from amputation to today’s treatment with surgery and preoperative and postoperative chemotherapy as the core,its cure rate has been greatly improved.However,the overall prognosis of osteosarcoma is still unsatisfactory because osteosarcoma is easily chemically resistant to the chemotherapy drugs during the preoperative and postoperative chemotherapy.A large amount of data shows that long non-coding RNA(lnc RNA)plays an important role in osteosarcoma,but its role in osteosarcoma resistance and its specific mechanism remain unclear.This topic focuses on the regulation of lnc RNA KCNQ1OT1 on the cisplatin resistance of osteosarcoma cells,and explores its effect on the basis of KCNQ1OT1 on the cell biological behavior of osteosarcoma cells and the effect on cisplatin resistance.The relationship with miR-335-5p/β-catenin axis and possible molecular mechanism.This experiment uses RT-qPCR,flow cytometry analysis,western blotting,transwell,dual luciferase reporter and other methods was analyzed.First,the regulation of KCNQ1OT1 on osteosarcoma cell biology and cisplatin resistance;then analyze the relationship between KCNQ1OT1 and miR-335-5p,miR-335-5p andβ-catenin,and its specific mechanism.Finally,the ectopic tumor formation experiment in nude mice was used to verify the effect of KCNQ1OT1 on OS resistance in vivo.The results showed that the expression of KCNQ1OT1 in osteosarcoma 143 B cells was significantly higher than that of the normal osteoblast cell line h FOB1.19,so did the expression of KCNQ1OT1 in cisplatin-resistant OS cells.KCNQ1OT1 is involved in a series of biological behaviors about the proliferation,cycle,apoptosis,migration and invasion of 143B/DDP cells.The resistance of143 B cells to cisplatin was inhibited by KCNQ1 OT knocking down through miR-335-5p.In addition,compared with osteoblasts,miR-335-5p is the most down-regulated miRNA in OS cells,and β-catenin expression was increased in 143B/DDP cells.The expression of β-catenin was significantly down-regulated by miR-335-5p mimics or sh-KCNQ1OT1,while the expression of β-catenin was increased after miR-335-5p inhibitor transfection.The results of this study indicate that KCNQ1OT1 can promote the cisplatin resistance in osteosarcoma cells,which may be mediated through the regulation of miR-335-5p/β-catenin axis.