Long Non-coding RNA DINO（Damage Induced Non-coding）Promotes Cisplatin Sensitivity Of Lung Adenocarcinoma Cancer Via P53-BAX Axis

BACKGROUNDIn China,lung cancer is the malignant cancer with the most new cases and deaths,and its main pathological type is non-small cell lung cancer（NSCLC）.The application of immunotherapy and targeted therapy offers new hope,but most patients are already in the intermediate and advanced stage when they are diagnosed.Currently,the first-line chemotherapy regimen for patients with advanced NSCLC is still mainly platinum-containing drugs.However,platinum-containing drugs resistance limits the efficacy of tumor treatment.Increasing studies have pointed out that LncRNAs are related to the effect of chemotherapy,suggesting that LncRNAs may be involved in the cisplatin treatment of lung adenocarcinoma.Long non-coding RNA（LncRNA）refers to a class of RNA with a length of over 200 nucleotides,and cannot encode a protein.Previous studies have found that when doxorubicin causes DNA damage in human cells,the expression of LncRNA DINO is up-regulated and participates in the response.Cisplatin treatment of tumors can also cause DNA damage,but whether LncRNA DINO is involved in the treatment of lung adenocarcinoma is still unknown.ObjectiveThis study clarified the role and clinical significance of LncRNA DINO in the treatment of lung adenocarcinoma with cisplatin.MethodsAnnoLnc database and qRT-PCR were used to detect the expression of LncRNA DINO in lung adenocarcinoma cell lines.We choose lung adenocarcinoma cell line A549 and cisplatin-resistant cell line A549R as cell models.This cell models were transfected with lentivirus to construct cells model overexpressing or interfering with LncRNA DINO.After cisplatin treatment,CCK8 and flow cytometry were used to detect the change of cell apoptosis rate.Perform enrichment analysis of differential genes and pathways in GEO and STRING databases.qRT-PCR and Western Blot detect the change of P53-BAX axis.Cycloheximide interference with nascent proteins proved that LncRNA DINO increased the stability of P53.Use plasmid to block the expression of P53 or BAX protein.After overexpression of LncRNA DINO,Western Blot was used to detect the change of P53-BAX axis,and flow cytometry to detect the apoptosis rate.In vivo experiments,nude mice were selected to undergo intraperitoneal injection of cisplatin after subcutaneous tumor formation.The diameter and weight of the tumor were recorded.After the tumor was removed,immunohistochemistry and HE stain were performed.Results1.The low expression of LncRNA DINO in lung adenocarcinoma cell lines.2.LncRNA DINO promotes the cisplatin sensitivity of lung adenocarcinoma.3.LncRNA DINO enhances the stability of P53 and mediates the activation of the P53-BAX axis.4.LncRNA DINO can partially reverse the cisplatin resistance after silencing the P53-BAX axis.5.LncRNA DINO inhibits the ability of nude mice to form subcutaneous tumors after cisplatin treatment.ConclusionExperiments have shown that LncRNA DINO stabilizes P53 to mediate the activation of the P53-BAX axis and regulate the chemotherapy sensitivity of lung adenocarcinoma to cisplatin.