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

摘要: Environmental chemicals exposure is one of the primary factors for liver toxicity and hepatocarcinoma. Thioacetamide (TAA) a well-known hepatotoxicant could be carcinogen in humans. The discovery early sensitive microRNA (miRNA) biomarkers injury tumor progression improve cancer diagnosis, prognosis, management. To study this, we performed next generation sequencing livers Sprague-Dawley rats treated with TAA at three doses (4.5, 15 45 mg/kg) four time points (3-, 7-, 14- 28-days). Overall, 330 unique differentially expressed miRNAs (DEMs) were identified entire TAA-treatment course. Of these, 129 DEMs found significantly enriched “liver cancer” annotation. These results further complemented by pathway analysis (Molecular Mechanisms Cancer, p53-, TGF-β-, MAPK- Wnt-signaling). Two (rno-miR-34a-5p rno-miR-455-3p) out 48 overlapping to TAA-induced hepatocarcinogenicity. We have shown significant regulatory associations between carcinogenesis an earlier stage than histopathological features. Most importantly, miR-34a-5p most suitable biomarker hepatocarcinogenesis due its consistent elevation during treatment