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

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...

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Vydané v:Scientific reports Ročník 7; číslo 1; s. 3054 - 12
Hlavní autori: Dweep, Harsh, Morikawa, Yuji, Gong, Binsheng, Yan, Jian, Liu, Zhichao, Chen, Tao, Bisgin, Halil, Zou, Wen, Hong, Huixiao, Shi, Tieliu, Gong, Ping, Castro, Christina, Uehara, Takeki, Wang, Yuping, Tong, Weida
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: London Nature Publishing Group UK 08.06.2017
Nature Publishing Group
Nature Portfolio
Predmet:
38/77
45
45/91
60 APPLIED LIFE SCIENCES
631/114/2163
631/154/53
631/337/384/331
631/61/514/2254
692/53
Animals
Biomarkers
Cancer
Carcinogenesis
Carcinogenesis - genetics
Hepatocellular carcinoma
Humanities and Social Sciences
Liver - metabolism
Liver cancer
Liver Neoplasms - etiology
Liver Neoplasms - genetics
Liver Neoplasms - pathology
Male
MAP kinase
MAP Kinase Signaling System
MicroRNAs - genetics
miRNA
Molecular modelling
multidisciplinary
p53 Protein
Rats
Rats, Sprague-Dawley
Rodents
Science
Science & Technology - Other Topics
Science (multidisciplinary)
Thioacetamide
Thioacetamide - toxicity
Toxicity
Wnt protein
Wnt Signaling Pathway
ISSN:2045-2322, 2045-2322
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Shrnutí: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.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
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USDOE
SC0014664
US Food and Drug Administration
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-02798-7