Long Non-coding RNA FAM83H-AS1 Promote Malignant Progression In Lung Adenocarcinoma

Background:Long non-coding RNA(lnc RNA)has been neglected in the past several years in cancer research.But now,amonuts of studies have demonstrated that lnc RNA is involved in various physiological and pathological processes and play an important role in the tumorigenesis,progression,metastasis and resistance of cancer cells.This study aims to thoroughly explore driver lnc RNA in lung adenocarcinoma(LUAD)and investigate molecular mechanisms.Methods:LUAD data project of the cancer genome atlas(TCGA)database is used to investigate copy number variation(CNV)and genes expression level in LUAD.Driver gene screening model is then built to search for driver lnc RNAs in LUAD.Weighted gene co-expression network analysis(WGCNA)is applied to validate screened lnc RNA FAM83H-AS1.Biological function of FAM83H-AS1 is investigated both in vitro and in vivo.RNA pull-down assay,RNA immunoprecipitation(RIP)assay and nucleus/cytoplasm separation assay are applied to classify the molecular mechanisms.In situ hybridization(ISH)assay is performed to investigate the association between FAM83H-AS1 and clinical characteristics.Results:Driver gene screening model based on CNV and gene expression level explores a potential driver lnc RNA FAM83H-AS1.WGCNA demonstrates that FAM83H-AS1 is associated with T stage related gene module in LUAD.Loss and gain of function studies demonstrated that suppression or overexpression of FAM83H-AS1 significantly regulates proliferation,transwell,invasion and apoptosis in LUAD cells.In vivo experiments show that silence of FAM83H-AS1 suppressed tumor formation in nude mice.RNA high through-put sequencing and mass spectrum are applied after silencing FAM83H-AS1 in LUAD cell lines.Significant protein level changes are detected instead of transcription levels.RNA pull-down assay,RNA immunoprecipitation(RIP)assay and nucleus/cytoplasm separation assay demonstrate that FAM83H-AS1 could bind hn RNPK to promotes translation of oncogene RAB8 B and RAB14 and malignant progression of LUAD cells.40 pairs LUAD RNA samples and 87 pairs LUAD tissue microarray are used to validate expression,T stage relevance and prognosis of FAM83H-AS1 in LUAD.Conclusion:In the current study,we discover a potential driver gene FAM83H-AS1 by building driver gene screening model and applying WGCNA.Studies in vitro and in vivo and molecular biology experiments elucidate that oncogene FAM83H-AS1 binds hn RNPK to promote translation of RAB8 B and RAB14.This study provides insights into the mechanism of malignant progression of LUAD and uncovered new targets for diagnosis and therapeutics of lung adenocarcinoma.