Kagoshima University · Division of Veterinary Medicine, School of Agriculture, Fisheries and Veterinary Medicine · 助教

Research keywordsveterinary pathology・canine cytology・feline pathology・immunocytochemistry・renal pathology・canine liver tumors・CLN3 mutation・diagnostic biomarkers

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• 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
• Omura K., Ide K., Takahashi M., Furusawa Y., Kobayashi M., Miyagawa Y., Fujiwara-Igarashi A., Teshima T., Kubo Y., Yasuda A., Yoshida K., Hayakawa N., Kobayashi M., Momoi Y. . Development of a2024 · 記述言語： 日本語 出版者・発行元： Veterinary and Animal Science In the veterinary field, the utility of disease-identification models that use comprehensive circulating microRNA (miRNA) profiles produced through measurements based on next-generation sequencing (NGS) remains unproven. To integrate NGS technology with automated machine learning (autoML) to create a comprehensive circulating miRNA profile and to assess the clinical utility of a disease-screening model derived from this profile. The study involved dogs diagnosed with or being treated for various diseases, including tumors, across multiple veterinary clinics (n = 254), and healthy dogs without apparent diseases (n = 91). miRNA was extracted from EDTA-treated plasma, and a comprehensive analysis was conducted of one million reads per sample using NGS. Then autoML technology was applied to develop a diagnostic model based on miRNA. Among these models, the one with the highest performance was chosen for evaluation. The diagnostic model, based on the comprehensive circulating miRNA profile developed in this study, achieved an AUC score of 0.89, with a sensitivity of 85 % and a specificity of 88 % for the disease samples. The miRNA-based diagnostic model demonstrated high sensitivity for disease groups and has the potential to be an effective screening test. This study indicates that a comprehensive miRNA profile in dog plasma could serve as a highly sensitive blood biomarker. DOI： 10.1016/j.vas.2024.100414 Scopus PubMed
• Kurahara N., Yutsudo A., Furusawa Y., Yamato O., Miyoshi N., Hifumi T., Yabuki A. . Immunohistochemical analysis of renal oxidative damage in senior and geriatric cats with chronic kidney dise2023 · 記述言語： 英語 出版者・発行元： Journal of Comparative Pathology Oxidative stress is a well-known cause of chronic kidney disease (CKD). In this study, renal oxidative damage in azotaemic and non-azotaemic aged cats with naturally occurring CKD was investigated using immunohistochemistry for 8-hydroxy-2′-deoxyguanosine (8-OHdG) and 4-hydroxynonenal (4-HNE) as markers of oxidative tissue damage. Kidneys were obtained from aged (>10 years old) azotaemic (n = 13) and non-azotaemic (n = 7) cats. Immunoreactivity for 8-OHdG was found in the nuclei of glomeruli, proximal and distal tubules, loops of Henle and collecting ducts, whereas 4-HNE-positive signals were detected in the cytoplasm of distal nephrons in azotaemic and non-azotaemic cats. Quantitative analysis did not identify any significant differences between the azotaemic and non-azotaemic groups for any of the parameters examined. These results indicate that renal oxidative damage occurs in the kidneys of aged cats with CKD, regardless of whether they are azotaemic or non-azotaemic, emphasizing the importance of oxidative stress during early-stage CKD in senior and geriatric cats. DOI： 10.1016/j.jcpa.2023.09.001 Scopus PubMed

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