Mechanistic roles of microRNAs in hepatocarcinogenesis: A study of thioacetamide with multiple doses and time-points of rats

Abstract Environmental chemicals exposure is one of the primary factors for liver toxicity and hepatocarcinoma. Thioacetamide (TAA) is a well-known hepatotoxicant and could be a liver carcinogen in humans. The discovery of early and sensitive microRNA (miRNA) biomarkers in liver injury and tumor pro...

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Autores principales:	Harsh Dweep, Yuji Morikawa, Binsheng Gong, Jian Yan, Zhichao Liu, Tao Chen, Halil Bisgin, Wen Zou, Huixiao Hong, Tieliu Shi, Ping Gong, Christina Castro, Takeki Uehara, Yuping Wang, Weida Tong
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fbe8d2ed9b374448a100bb4a54a29912
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spelling	oai:doaj.org-article:fbe8d2ed9b374448a100bb4a54a299122021-12-02T11:41:22ZMechanistic roles of microRNAs in hepatocarcinogenesis: A study of thioacetamide with multiple doses and time-points of rats10.1038/s41598-017-02798-72045-2322https://doaj.org/article/fbe8d2ed9b374448a100bb4a54a299122017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02798-7https://doaj.org/toc/2045-2322Abstract Environmental chemicals exposure is one of the primary factors for liver toxicity and hepatocarcinoma. Thioacetamide (TAA) is a well-known hepatotoxicant and could be a liver carcinogen in humans. The discovery of early and sensitive microRNA (miRNA) biomarkers in liver injury and tumor progression could improve cancer diagnosis, prognosis, and management. To study this, we performed next generation sequencing of the livers of Sprague-Dawley rats treated with TAA at three doses (4.5, 15 and 45 mg/kg) and four time points (3-, 7-, 14- and 28-days). Overall, 330 unique differentially expressed miRNAs (DEMs) were identified in the entire TAA-treatment course. Of these, 129 DEMs were found significantly enriched for the “liver cancer” annotation. These results were further complemented by pathway analysis (Molecular Mechanisms of Cancer, p53-, TGF-β-, MAPK- and Wnt-signaling). Two miRNAs (rno-miR-34a-5p and rno-miR-455-3p) out of 48 overlapping DEMs were identified to be early and sensitive biomarkers for TAA-induced hepatocarcinogenicity. We have shown significant regulatory associations between DEMs and TAA-induced liver carcinogenesis at an earlier stage than histopathological features. Most importantly, miR-34a-5p is the most suitable early and sensitive biomarker for TAA-induced hepatocarcinogenesis due to its consistent elevation during the entire treatment course.Harsh DweepYuji MorikawaBinsheng GongJian YanZhichao LiuTao ChenHalil BisginWen ZouHuixiao HongTieliu ShiPing GongChristina CastroTakeki UeharaYuping WangWeida TongNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Harsh Dweep Yuji Morikawa Binsheng Gong Jian Yan Zhichao Liu Tao Chen Halil Bisgin Wen Zou Huixiao Hong Tieliu Shi Ping Gong Christina Castro Takeki Uehara Yuping Wang Weida Tong Mechanistic roles of microRNAs in hepatocarcinogenesis: A study of thioacetamide with multiple doses and time-points of rats
description	Abstract Environmental chemicals exposure is one of the primary factors for liver toxicity and hepatocarcinoma. Thioacetamide (TAA) is a well-known hepatotoxicant and could be a liver carcinogen in humans. The discovery of early and sensitive microRNA (miRNA) biomarkers in liver injury and tumor progression could improve cancer diagnosis, prognosis, and management. To study this, we performed next generation sequencing of the livers of Sprague-Dawley rats treated with TAA at three doses (4.5, 15 and 45 mg/kg) and four time points (3-, 7-, 14- and 28-days). Overall, 330 unique differentially expressed miRNAs (DEMs) were identified in the entire TAA-treatment course. Of these, 129 DEMs were found significantly enriched for the “liver cancer” annotation. These results were further complemented by pathway analysis (Molecular Mechanisms of Cancer, p53-, TGF-β-, MAPK- and Wnt-signaling). Two miRNAs (rno-miR-34a-5p and rno-miR-455-3p) out of 48 overlapping DEMs were identified to be early and sensitive biomarkers for TAA-induced hepatocarcinogenicity. We have shown significant regulatory associations between DEMs and TAA-induced liver carcinogenesis at an earlier stage than histopathological features. Most importantly, miR-34a-5p is the most suitable early and sensitive biomarker for TAA-induced hepatocarcinogenesis due to its consistent elevation during the entire treatment course.
format	article
author	Harsh Dweep Yuji Morikawa Binsheng Gong Jian Yan Zhichao Liu Tao Chen Halil Bisgin Wen Zou Huixiao Hong Tieliu Shi Ping Gong Christina Castro Takeki Uehara Yuping Wang Weida Tong
author_facet	Harsh Dweep Yuji Morikawa Binsheng Gong Jian Yan Zhichao Liu Tao Chen Halil Bisgin Wen Zou Huixiao Hong Tieliu Shi Ping Gong Christina Castro Takeki Uehara Yuping Wang Weida Tong
author_sort	Harsh Dweep
title	Mechanistic roles of microRNAs in hepatocarcinogenesis: A study of thioacetamide with multiple doses and time-points of rats
title_short	Mechanistic roles of microRNAs in hepatocarcinogenesis: A study of thioacetamide with multiple doses and time-points of rats
title_full	Mechanistic roles of microRNAs in hepatocarcinogenesis: A study of thioacetamide with multiple doses and time-points of rats
title_fullStr	Mechanistic roles of microRNAs in hepatocarcinogenesis: A study of thioacetamide with multiple doses and time-points of rats
title_full_unstemmed	Mechanistic roles of microRNAs in hepatocarcinogenesis: A study of thioacetamide with multiple doses and time-points of rats
title_sort	mechanistic roles of micrornas in hepatocarcinogenesis: a study of thioacetamide with multiple doses and time-points of rats
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/fbe8d2ed9b374448a100bb4a54a29912
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Mechanistic roles of microRNAs in hepatocarcinogenesis: A study of thioacetamide with multiple doses and time-points of rats

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