• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Scientific Publications by FDA Staff

  • Print
  • Share
  • E-mail

Search Publications



Starting Date

Ending Date

Order by

Entry Details

Sci Rep 2017 Jun 8;7(1):3054

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

Dweep H, Morikawa Y, Gong B, Yan J, Liu Z, Chen T, Bisgin H, Zou W, Hong H, Shi T, Gong P, Castro C, Uehara T, Wang Y, Tong W


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-beta-, 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.

Category: Journal Article
PubMed ID: #28596526 DOI: 10.1038/s41598-017-02798-7
PubMed Central ID: #PMC5465221
Includes FDA Authors from Scientific Area(s): Toxicological Research
Entry Created: 2017-06-11 Entry Last Modified: 2017-06-25