Results showed that the deregulated piRNAs identified here can target multiple signaling pathways, including death and TNF receptors, HIPPO, p53, PI3K/AKT, WNT/β-catenin, GADD45, AMPK, HMGB1 and PTEN pathways (Supplementary Figure S3B and Supplementary Table S8), that control, among others, cell cycle regulation, telomerase activity, protein ubiquitination, DNA methylation and apoptosis, all functions compromised in HCC. This evidence concerns the gene GADD45A and hepatocellular carcinoma.