LncRNA ANCR Promotes Hepatocellular Carcinoma Metastasis Through Upregulating HNRNPA1 Expression

Background/Aims:LncRNA ANCR plays important roles in the modulation of epithelial mesenchymal transition(EMT)and tumor metastasis in many tumors.However,the role of ANCR in regulating hepatocellular carcinoma(HCC)metastasis is still not known.The current study aims to investigate the underlying mechanism for tumor oncogenesis of ANCR in HCC metastasis.Methods:HCC cell proliferation and migration/invasion weremeasured by MTT and Transwell assays.Xenograft model was established to determine the effect ofANCR on HCC growth and metastasis.ChIP assay was used to detect the H3 and H4 histone acetylationlevels at the ANCR promoter region.RNA pull-down and RIP assay was performed to analyse therelationship between ANCR and heterogeneous nuclear ribonucleoprotein A1(HNRNPA1).Dualluciferasereporter gene assay was conducted to determine the interaction between ANCR and miR-140-3p.Results:The results indicated that ANCR was highly expressed in HCC tissues and cells,which promotedthe proliferation and migration/invasion of HCC cells.In vivo experiments showed interfering ANCR supressed the growth and metastasis of HCC.H3/H4 histone acetylation levels at the ANCR promoterregion were elevated in HCC tissues and cells,and interfering histone deacetylases 3(HDAC3)significantly up-regulated ANCR expression.ANCR could bind to HNRNPA1,and promoted the expression of HNRNPA1 through regulating its degradation.In addition,ANCR upregulated the expression of HNRNPA1 through sponging miR-140-3p.Finally,we found that ANCR promoted the EMT and invasion/migration of HCC cells through regulating HNRNPA1.Conclusion:LncRNA ANCR promoted HCC metastasisby upregulating HNRNPA1,inhibiting HNRNPA1 degradation and sponging miR-140-3p.