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微小RNA及miR-1/MET信号通路在犬肝细胞癌中的异常表达

Aberrant expression of microRNAs and the miR-1/MET pathway in canine hepatocellular carcinoma.

作者信息

Lai Y-C, Ushio N, Rahman M M, Katanoda Y, Ogihara K, Naya Y, Moriyama A, Iwanaga T, Saitoh Y, Sogawa T, Sunaga T, Momoi Y, Izumi H, Miyoshi N, Endo Y, Fujiki M, Kawaguchi H, Miura N

机构信息

Veterinary Teaching Hospital, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan.

The United Graduate School of Veterinary Science, Yamaguchi University, Yamaguchi, Japan.

出版信息

Vet Comp Oncol. 2018 Jun;16(2):288-296. doi: 10.1111/vco.12379. Epub 2018 Jan 3.

DOI:10.1111/vco.12379
PMID:29314614
Abstract

Canine hepatocellular carcinoma (HCC) is the most common primary hepatic tumour in dogs. MicroRNA (miRNA) dysregulation has been reported in human HCC and shown to have diagnostic and prognostic value; however, there are no data on miRNA expression in canine HCC. The aim of the present study was to investigate differentially expressed miRNAs in canine HCC. Analysis of miRNA expression in canine HCC tissues and cell lines by quantitative reverse transcription PCR showed that miR-1, miR-122, let-7a, and let-7g were downregulated, whereas miR-10b and miR-21 were upregulated in canine HCC. MET is one of the target genes of miR-1. MET was upregulated in canine HCC at the gene and protein levels, and a significant correlation between the concomitant downregulation of miR-1 and upregulation of MET was observed. Fast/intermediate-proliferating canine HCC cell lines had higher MET gene and protein expression levels than the slow-proliferating cell line. These findings suggest that miRNAs are differentially expressed in canine HCC, and that the miR-1/MET pathway may be associated with canine HCC cell proliferation.

摘要

犬肝细胞癌(HCC)是犬类最常见的原发性肝脏肿瘤。据报道,人类HCC中存在微小RNA(miRNA)失调,且显示出具有诊断和预后价值;然而,关于犬HCC中miRNA表达的数据尚无。本研究的目的是调查犬HCC中差异表达的miRNA。通过定量逆转录PCR分析犬HCC组织和细胞系中的miRNA表达,结果显示,在犬HCC中,miR-1、miR-122、let-7a和let-7g表达下调,而miR-10b和miR-21表达上调。MET是miR-1的靶基因之一。在犬HCC中,MET在基因和蛋白水平均上调,且观察到miR-1的伴随下调与MET的上调之间存在显著相关性。快速/中等增殖的犬HCC细胞系比缓慢增殖的细胞系具有更高的MET基因和蛋白表达水平。这些发现表明,miRNA在犬HCC中存在差异表达,且miR-1/MET通路可能与犬HCC细胞增殖有关。

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