LincRNA00844 Exerts Tumor Inhibitory Effect Via Regulating MAPK Pathway By AZGP1 In Hepatocellular Carcinoma

Background:Increasing proofs have demonstrated that aberrant expression of long noncoding RNAs(lnc RNA)appeared in multiple cancers and gave rise to their deterioration.This study intended to investigate the role of linc RNA00844 in hepatocellular carcinoma(HCC).Methods and Materials Gene expression of linc RNA00844 was determined by quantitative real-time PCR(q PCR).All protein level associated were detected with Western Blotting assays.The function of linc RNA00844 was observed through cell viability assay,colony formation assay,Edu assays,cell cycle analysis,apoptosis detection and transwell assay in vitro and tumorigenesis experiment in vivo.The correlation between linc RNA00844 contains and survival outcomes was identified with Cox proportional hazards model.KEGG analysis was adopted to decode associated gene expression alterations on signaling pathways.Underlying mechanism was revealed through exerting mass spectrometry analysis and RNA pull-down assay.Results:LincRNA00844 was remarkably downregulated in HCC tissues compared to adjacenttissues,and low expression level of LincRNA00844 was associated with poor clinical prognosis.Besides,inferior tumor characteristics including portal vein invasion,high AFP level and elevated tumor recurrence were related to function loss of linc RNA00844.Ectopic linc RNA00844 expression in HCC cell lines tremendously suppressed proliferation,migration as well as invasion,while linc RNA00844 deletion resulted in progressed proliferation rate as well as migration behavior.Cell cycle in HCC cells within more LincRNA00844 expression were arrested in G1 phase,and vice versa.In vivo,linc RNA00844 precipitously cut down the tumorigenesis ability of HCC cells.Signaling pathways analysis results indicated that MAPK signaling pathway was at most disturbed by linc RNA00844.Western blotting assay confirmed that both p-MEK and p-ERK levels were inhibited by linc RNA00844,along with cyclin D1 and CDK4.Subsequent mass spectrometry analysis RNA-pull down assay detected an physical interaction between LincRNA00844 and zinc α-2 glycoprotein.Deletion of zinc α-2 glycoprotein restored G1 arresting effect induced by linc RNA00844.Conclusion:LincRNA00844 is a meaningful prognostic predictor for HCC patients with or without liver transplantation,inactivation of TGF-β1 induced MAPK pathways is a promising therapeutic target on the way contending against HCC.