Exploration of m6 A-Related lncRNAs and the Role of DACH1 in Prognosis and Immune Characteristics of Hepatocellular Carcinoma
This study aimed to investigate the impact of N6-methyladenosine(m6A)-related long non-coding RNAs(LncRNAs)and Dachshund homolog 1(DACH1)on the prognosis and immune infiltration of hepatocel-lular carcinoma(HCC).Using bioinformatics,we constructed a risk model involving DACH1 and m6A-related LncRNAs,conducted clustering analysis,immune infiltration,and tumor microenvironment(TME)analysis,and evaluated the risk scores and clinical correlations.The results showed that 56 m6A-related LncRNAs were in-volved in the progression of HCC.Through univariate,multivariate,and LASSO regression analyses,11 m6A-re-lated LncRNAs most correlated with DACH1 expression were identified,including AC027097.1,LINC01138,LINC01224,DDX11-AS1,MKLN1-AS,AL031985.3,AC098484.1,AL158166.1,POLH-AS1,WAC-AS1,and NRAV.These LncRNAs were closely associated with immune cell infiltration.Further RT-qPCR,Western blot(WB),and immunohistochemistry(IHC)experiments revealed that DACH1 mRNA expression in HCC cells was significantly lower than that in normal hepatocytes,and the DACH1 protein expression in normal liver cells and tissues was notably higher than in HCC cells.Additionally,treatment of HCC cells with 5-aza-2dc(a methylation inhibitor)significantly reduced cell migration distance,suggesting that DACH1 demethylation might enhance its tumor-suppressing function.Through bioinformatics analysis and experimental validation,this study identified 11 m6A-modified LncRNAs associated with DACH1 expression,highlighting the crucial role of DACH1 in HCC progression,development,and immune infiltration,providing theoretical support for the early di-agnosis and prognosis of HCC.