miR-26a-5p protects against drug-induced liver injury via targeting bid.

BACKGROUNDS: miR-26a-5p is a short noncoding RNA that is abnormally expressed in drug-induced liver injury (DILI), but its pathophysiologic role in the mechanism of disease in DILI is still vague. METHODS: The expression of miR-26a-5p, viability of hepatic stellate cells (HSCs) proliferation, and apoptosis were explored via real-time PCR, CCK-8 assay, Tunel fluorescence, and flow cytometry. The expression of Bid was detected via Western blot assays, real-time PCR, and immunofluorescence. The apoptosis-associated proteins were determined through Western blot. The interaction between miR-26a-5p and Bid was measured via Dual luciferase reporter assay. RESULTS: miR-26a-5p expression was greatly decreased in HSCs and serum treated with azithromycin, simvastatin and diclofenac sodium, respectively. Hepatocyte viability was largely suppressed while hepatocyte apoptosis was markedly increased in DILI. Correspondingly, the apoptosis-associated proteins including Bid, caspase-8 and cytochrome C in HSCs were significantly upregulated when treated with either of these drugs. Moreover, miR-26a-5p interacted with Bid, and hepatocyte proliferation and apoptosis influenced by miR-26a-5p mimics were obviously reversed when co-treated with overexpressed Bid plasmids. CONCLUSIONS: miR-26a-5p played a protective role against DILI via targeting Bid.