Identification of pyroptosis-associated miRNAs in the immunoscape and prognosis of hepatocellular carcinoma.

BACKGROUND

Hepatocellular carcinoma is one of the most prevalent types of liver malignancy and poses a severe threat to global health. Despite recent improvements in therapeutic approaches, treatment options for patients with advanced or recurrent HCC are still limited.

MATERIALS AND METHODS

Our study analyzed miRNA differential expression using data from hepatocellular carcinoma patients in the Cancer Genome Atlas. Pyroptosis-related genes were identified from gene cards. Differential expression of miRNAs was analyzed using DESeq2 and visualized using ggplot2 and pheatmap. A prognostic risk model for pyroptosis-associated miRNAs was constructed using LASSO regression and validated by principal component analysis, Kaplan-Meier survival and ROC curve analysis. We also performed gene and pathway enrichment analysis. Immune cell infiltration and function in HCC were assessed using single-sample genomic enrichment analysis, and correlations with immune cells and function were explored. Also, CCK-8 assay as well as migration and invasion assays were performed after knockdown of miR-6844.

RESULTS

We have established and validated a prognostic risk model based on ten DEmiRNAs, which is important for the survival of HCC patients. Significant changes in immune cell infiltration and immune function were also found in high-risk patients. It also demonstrated that knockdown of miR-6844 inhibited HCC cell proliferation, migration and invasion, highlighting its role in HCC progression.

CONCLUSION

Our study reveals the implications of pyroptosis-associated differential miRNAs on the prognosis of patients with hepatocellular carcinoma and provides a foundation for novel HCC therapies, especially immunotherapy.