Identification of dysregulated miRNA transcriptomic profile in canine hepatocellular carcinoma and comparison to human HCC.

Abstract

Hepatocellular carcinoma (HCC) is the most common liver tumor in dogs. MicroRNA (miRNA) dysregulation and its clinical significance have been reported in dog and human cancers, including HCC. However, determining the whole miRNA transcriptomic profile is essential for diagnosis and therapeutics. Here, we determined the miRNA transcriptomic profile of canine HCC. First, miRNA expression from three control liver tissues and three canine HCC patients was analyzed via small RNA next-generation sequencing (NGS). After analyzing the sequencing reads, differential miRNA (DEmiRNA) expression was further confirmed in the clinical samples and three HCC cell lines via qRT-PCR. The functional pathways of the DEmiRNAs were analyzed from an experimentally validated human miRNA-target database. Our study revealed 20 upregulated and nine downregulated miRNAs. Among them, 10 miRNAs were further validated by qRT-PCR. qRT-PCR and NGS revealed similar miRNA expression patterns. Furthermore, we investigated the signaling pathways based on the KEGG pathway analysis and performed a functional analysis of the dysregulated miRNAs in canine HCC. The upregulated miRNAs mainly play a role in the p53 and cell cycle pathways and function in DNA damage repair and differentiation. In contrast, the downregulated miRNAs are involved in cancer and cell cycle pathways and mainly function in cell differentiation. Further, these miRNAs may be investigated in light of miRNA-based diagnosis and therapies.