DARS2 Targeting ERK/c-Myc Signaling Pathway Promotes The Occurrence And Development Of Lung Adenocarcinoma

BackgroundThe incidence of cancer is increasing worldwide and is becoming the most common cause of death.It is now widely believed that cancer is a complex disease composed of multiple histological and molecular types.Lung adenocarcinoma is a major malignant tumor and one of the most common cancer-related deaths in the world,although great efforts have been made to improve early detection and develop new ones.In terms of treatment strategy,patients with lung adenocarcinoma still face the problems of high postoperative recurrence rate and poor survival rate.Therefore,it is necessary to find new molecular targets to improve the treatment of lung adenocarcinoma and predict the prognosis of lung adenocarcinoma patients.MethodsIn this study,we used the online database Timer 2.0 to analyze the expression of DARS2 in cancer patients.In addition,the clinical data of lung adenocarcinoma in The Cancer Genome Atlas(TCGA)was analyzed through the UALCAN database.The results showed that the expression of DARS2 in lung adenocarcinoma tissue was significantly higher than that in normal tissue.At the same time,the Kaplan-Meier curve drawn showed that the survival prognosis of lung adenocarcinoma patients with high expression of DARS2 was significantly worse than that of patients with low expression of DARS2.We detected the expression of DARS2 in lung adenocarcinoma tissues and adjacent normal tissues by immunohistochemical staining,and performed histochemical scoring and drew survival curve.In addition,the protein level of DARS2 in lung adenocarcinoma cell line was detected by Western blot.The knockdown and overexpression DARS2 cell lines and corresponding control group cell lines were constructed by small interference and overexpression virus.Through CCK-8 assay,EdU assay,wound healing assay,Transwell assay and Western Blot assay,the effects of DARS2 on proliferation,migration and invasion of lung adenocarcinoma cells and epithelial-mesenchymal transformation were explored.In addition,in order to further verify the carcinogenic effect of DARS2,we carried out the subcutaneous tumorigenesis assay in nude mice,and injected the lung adenocarcinoma cell lines with knockdown and overexpression of DARS2 and the cell lines of its control group into the armpit of nude mice.Finally,by knocking down and overexpressing DARS2 in lung adenocarcinoma cells and their control cells,Western Blot experiments were conducted to detect relevant indicators and adding pathway inhibitors for response experiments,further exploring and verifying the signaling pathway targeted by DARS2 in lung adenocarcinoma.ResultsThe expression of DARS2 was significantly upregulated in lung adenocarcinoma tissues and lung adenocarcinoma cell lines.At the same time,the increased expression of DARS2 is closely related to the worse prognosis of patients with lung adenocarcinoma.In addition,through relevant functional experiments,it was found that the high expression of DARS2 is closely related to the proliferation,invasion,and metastasis of lung adenocarcinoma cells.The nude mouse tumorigenesis experiment further showed that with the increase in the expression of DARS2,the tumorigenicity of the lung adenocarcinoma cell line in nude mice was significantly improved.Finally,through further research,we found that DARS2 plays a role in lung adenocarcinoma cell lines by targeting the ERK/c-Myc signaling pathway.ConclusionDARS2 targets ERK/c-Myc signal pathway to promote the occurrence and development of lung adenocarcinoma.