HNRNPLL is a Prognostic Biomarker Associated with Hepatocellular Carcinoma Immune Infiltration and Related to Migration of Hepatocellular Carcinoma Cells

Abstract

Background Heterogeneous nuclear ribonucleoprotein L-like (HNRNPLL) have a critical role in colorectal cancer progression and development. Althouh, the functions of HNRNPLLin liver hepatocellular carcinoma (LIHC) remain unclear. Methods Data from three databases, namely, Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and International Cancer Genome Consortium (ICGC), as well as tissue microarray (TMA) data were used to investigate the correlation of HNRNPLL expression, clinical features, and prognosis. The Tumor Immune Single-cell Hub (TISCH) website was utilized to examine the relationship between various HNRNPLLmethylation sites and LIHC prognosis and clinical features. CIBERSORT and quanTIseq were used to quantify the immune infiltration level in LIHC. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, Gene Ontology (GO) analysis, and gene set enrichment analysis (GSEA) were used to predict the gene function of HNRNPLL. Least absolute shrinkage and selection operator (LASSO) were utilized to construct a prognostic model. Eventually, the impact of HNRNPLL on migration and cell cycle were validated in two hepatocellular carcinoma cell lines, namely, Huh7 and HepG2, using scratch and flow cytometry. Results The findings indicated that highest levels of HNRNPLL mRNA and high levels of methylation were significantly connected to lower clinical stage and prognosis. The HNRNPLL expression was significantly positively associated with a variety of immune cells, especially regulatory T cells (Tregs), and the methylation of HNRNPLL was significantly positively associated with M2 macrophages. Finally, receiver operating characteristic (ROC) and decision curve analysis (DCA) curves verified the predictive model based on a protein interaction network had a good prognostic effect. By inhibiting the expression of HNRNPLL, we confirmed that downregulation of HNRNPLL partially reduced the invasion of Huh7 and HepG2 cells. Further, cell cycle was significantly inhibited by siRNA interference of HNRNPLL. Conclusion These findings indicated that HNRNPLL is a potential prognostic marker as its expression is significantly positively correlated with Tregs and its methylation status is significantly positively correlated with M2 macrophages. RNA interferes with its expression and has certain effects on cell cycle, migration and invasion.