ARCN1 Facilitates Tumor Growth And Metastasis Via Activating PI3K/AKT/mTOR Pathway In Human Lung Adenocarcinoma

BackgroundThe mortality rate of lung cancer is the highest in the world,with a low overall survival rate.The most familiar subtype of lung cancer is lung adenocarcinoma(LUAD).With the progress of science and technology and development of society,the treatment methods for lung cancer have become diverse and changing with each passing day.One of the hottest areas of research is targeted therapy right now.In this case,unremitting research to find new targets for the treatment of LUAD is very helpful to improve the therapeutic effect of LUAD patients.Based on published papers,we know that ARCN1 significantly inhibits the growth of a variety of cancer cell lines,including gastric cancer,ovarian cancer and HER+positive breast cancer.The purpose of this study was to investigate the role of ARCN1 in LUAD.MethodsIn this study,we analyzed clinical data of LUAD patients downloaded from the Cancer Genome Atlas(TCGA).In addition,Kaplan-Meier curves were plotted using survival data in Gene Expression Profiling Interactive Analysis(GEPIA)to show the correlation between the expression level of ARCN1 and the overall survival rate of LUAD patients.We detected the expression of ARCN1 in LUAD and adjacent non-tumor tissues by immunohistochemical staining(IHC)and Western Blot.We used quantitative real-time polymerase chain reaction(qRT-PCR)and Western Blot to detect the mRNA and protein expression of ARCN1 in LUAD cell lines.Lentiviral transfection was used to obtain ARCN1 overexpressed and knockdown stable strain cells and control cells,and the effects of ARCN 1 on proliferation,migration,invasion and epithelial mesenchymal transformation(EMT)of LUAD cells were verified by CCK8,Colon formation assay,EdU,wound healing,Transwell and Western Blot.To observe the effects of ARCN1 in vivo conditions,we subcutaneously injected stable knockdown of ARCN l(sh-ARCN1)and control(sh-NC)cells into young nude mice at once.Transcriptome sequencing analysis and Western Blot analysis were performed to discover the signaling pathway targeted by ARCN1.ResultsThe expression of ARCN1 is elevated in LUAD tissues and cell lines and associated with poor prognosis.ARCN1 promotes the proliferation,migration and invasion of LUAD cells and EMT.ARCN1 promotes the tumorigenicity of LUAD cells in vivo.ARCN1 affect the PI3K/AKT/mTOR signaling pathway to perform its biological functions.ConclusionARCN1 facilitates tumor growth and metastasis via activating PI3K/AKT/mTOR pathway in human lung adenocarcinoma.