Hashimoto S., Hasan M.D.N., Arif M., Nozaki N., Husna A.A., Furusawa Y., Sogawa T., Takahashi K., Kuramoto T., Noguchi A., Takahashi M., Rahman M.M., Miura N. . Identification of dysregulated2025 · 記述言語： 日本語 出版者・発行元： Research in Veterinary Science 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. DOI： 10.1016/j.rvsc.2025.105903 Scopus PubMed
Hashimoto S., Hasan M.N., Arif M., Nozaki N., Husna A.A., Furusawa Y., Sogawa T., Takahashi K., Kuramoto T., Noguchi A., Takahashi M., Yamato O., Rahman M.M., Miura N. . Aberrantly Expressed t2025 · 記述言語： 日本語 出版者・発行元： Genes Hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC) can be difficult to differentiate but must be diagnosed correctly as treatment and prognosis for these tumors differ markedly. Relevant diagnostic biomarkers are thus needed, and those identified in dogs may have utility in human medicine because of the similarities between human and canine HCA and HCC. A tRNA-derived fragment (tRF), tRNA-Val, is a promising potential biomarker for canine mammary gland tumors but has not previously been investigated in hepatic tumors. Accordingly, we aimed to elucidate the potential utility of tRNA-Val as a biomarker for canine HCA and HCC using clinical samples (tumor tissue and plasma extracellular vesicles [EVs]) and tumor cell lines with qRT-PCR assays. We also investigated relevant functions and signaling pathways with bioinformatic analyses (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes). tRNA-Val was markedly downregulated in HCC tumor tissue versus HCA tumor tissue and normal liver tissue, and a similar trend was shown in plasma EVs and HCC cell lines versus healthy controls. Based on areas under the receiver operating characteristic curves (AUCs), tRNA-Val significantly distinguished HCC (AUC = 1.00, p = 0.001) from healthy controls in plasma EVs and HCC from HCA (AUC = 0.950, p = 0.01). Bioinformatics analysis revealed that tRNA-Val may be primarily involved in DNA repair, mRNA processing, and splicing and may be linked to the N-glycan and ubiquitin-mediated proteasome pathways. This is the first report on the expression of tRNA-Val in canine HCC and HCA and its possible functions and signaling pathways. We suggest that tRNA-Val could be a promising novel biomarker to distinguish canine HCC from HCA. This study provides evidence for a greater understanding of the role played by tRNA-Val in the development of canine HCC. DOI： 10.3390/genes15081024 Scopus PubMed
