Comprehensive analysis of liver and blood miRNA in precancerous conditions

Abstract Streptozotocin administration to mice (STZ-mice) induces type I diabetes and hepatocellular carcinoma (HCC). We attempted to elucidate the carcinogenic mechanism and the miRNA expression status in the liver and blood during the precancerous state. Serum and liver tissues were collected from...

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Autores principales:	Tomohiro Umezu, Koichi Tsuneyama, Kohsuke Kanekura, Michiyo Hayakawa, Toshihito Tanahashi, Mitsuoki Kawano, Y-h Taguchi, Hidenori Toyoda, Akihiro Tamori, Masahiko Kuroda, Yoshiki Murakami
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6e8ef58c5f4a476882df1d08ac5d8698
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spelling	oai:doaj.org-article:6e8ef58c5f4a476882df1d08ac5d86982021-12-02T12:33:05ZComprehensive analysis of liver and blood miRNA in precancerous conditions10.1038/s41598-020-78500-12045-2322https://doaj.org/article/6e8ef58c5f4a476882df1d08ac5d86982020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78500-1https://doaj.org/toc/2045-2322Abstract Streptozotocin administration to mice (STZ-mice) induces type I diabetes and hepatocellular carcinoma (HCC). We attempted to elucidate the carcinogenic mechanism and the miRNA expression status in the liver and blood during the precancerous state. Serum and liver tissues were collected from STZ-mice and non-treated mice (CTL-mice) at 6, 10, and 12 W. The exosome enriched fraction extracted from serum was used. Hepatic histological examination and hepatic and exosomal miRNA expression analysis were serially performed using next-generation sequencing (NGS). Human miRNA expression analysis of chronic hepatitis liver tissue and exosomes, which were collected before starting the antiviral treatment, were also performed. No inflammation or fibrosis was found in the liver of CTL-mice during the observation period. In STZ-mice, regeneration and inflammation of hepatocytes was found at 6 W and nodules of atypical hepatocytes were found at 10 and 12 W. In the liver tissue, during 6–12 W, the expression levels of let-7f-5p, miR-143-3p, 148a-3p, 191-5p, 192-5p, 21a-5p, 22-3p, 26a-5p, and 92a-3p was significantly increased in STZ-mice, and anti-oncogenes of their target gene candidates were down-regulated. miR-122-5p was also significantly down-regulated in STZ-mice. Fifteen exosomal miRNAs were upregulated in STZ-mice. Six miRNAs (let-7f-5p, miR-10b-5p, 143-3p, 191-5p, 21a-5p, and 26a-5p) were upregulated, similarly to human HCC cases. From the precancerous state, aberrant expression of hepatic miRNAs has already occurred, and then, it can promote carcinogenesis. In exosomes, the expression pattern of common miRNAs between mice and humans before carcinogenesis was observed and can be expected to be developed as a cancer predictive marker.Tomohiro UmezuKoichi TsuneyamaKohsuke KanekuraMichiyo HayakawaToshihito TanahashiMitsuoki KawanoY-h TaguchiHidenori ToyodaAkihiro TamoriMasahiko KurodaYoshiki MurakamiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-11 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tomohiro Umezu Koichi Tsuneyama Kohsuke Kanekura Michiyo Hayakawa Toshihito Tanahashi Mitsuoki Kawano Y-h Taguchi Hidenori Toyoda Akihiro Tamori Masahiko Kuroda Yoshiki Murakami Comprehensive analysis of liver and blood miRNA in precancerous conditions
description	Abstract Streptozotocin administration to mice (STZ-mice) induces type I diabetes and hepatocellular carcinoma (HCC). We attempted to elucidate the carcinogenic mechanism and the miRNA expression status in the liver and blood during the precancerous state. Serum and liver tissues were collected from STZ-mice and non-treated mice (CTL-mice) at 6, 10, and 12 W. The exosome enriched fraction extracted from serum was used. Hepatic histological examination and hepatic and exosomal miRNA expression analysis were serially performed using next-generation sequencing (NGS). Human miRNA expression analysis of chronic hepatitis liver tissue and exosomes, which were collected before starting the antiviral treatment, were also performed. No inflammation or fibrosis was found in the liver of CTL-mice during the observation period. In STZ-mice, regeneration and inflammation of hepatocytes was found at 6 W and nodules of atypical hepatocytes were found at 10 and 12 W. In the liver tissue, during 6–12 W, the expression levels of let-7f-5p, miR-143-3p, 148a-3p, 191-5p, 192-5p, 21a-5p, 22-3p, 26a-5p, and 92a-3p was significantly increased in STZ-mice, and anti-oncogenes of their target gene candidates were down-regulated. miR-122-5p was also significantly down-regulated in STZ-mice. Fifteen exosomal miRNAs were upregulated in STZ-mice. Six miRNAs (let-7f-5p, miR-10b-5p, 143-3p, 191-5p, 21a-5p, and 26a-5p) were upregulated, similarly to human HCC cases. From the precancerous state, aberrant expression of hepatic miRNAs has already occurred, and then, it can promote carcinogenesis. In exosomes, the expression pattern of common miRNAs between mice and humans before carcinogenesis was observed and can be expected to be developed as a cancer predictive marker.
format	article
author	Tomohiro Umezu Koichi Tsuneyama Kohsuke Kanekura Michiyo Hayakawa Toshihito Tanahashi Mitsuoki Kawano Y-h Taguchi Hidenori Toyoda Akihiro Tamori Masahiko Kuroda Yoshiki Murakami
author_facet	Tomohiro Umezu Koichi Tsuneyama Kohsuke Kanekura Michiyo Hayakawa Toshihito Tanahashi Mitsuoki Kawano Y-h Taguchi Hidenori Toyoda Akihiro Tamori Masahiko Kuroda Yoshiki Murakami
author_sort	Tomohiro Umezu
title	Comprehensive analysis of liver and blood miRNA in precancerous conditions
title_short	Comprehensive analysis of liver and blood miRNA in precancerous conditions
title_full	Comprehensive analysis of liver and blood miRNA in precancerous conditions
title_fullStr	Comprehensive analysis of liver and blood miRNA in precancerous conditions
title_full_unstemmed	Comprehensive analysis of liver and blood miRNA in precancerous conditions
title_sort	comprehensive analysis of liver and blood mirna in precancerous conditions
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/6e8ef58c5f4a476882df1d08ac5d8698
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Comprehensive analysis of liver and blood miRNA in precancerous conditions

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