Fig. 8.

Schematic diagram of the proposed role of miR-34a in PA-induced cholangiocyte lipoapoptosis. The saturated FFA, PA, increased nuclear FoxO3 levels leading to increased miR-34a in PA-treated cells. miR-34a then promoted lipoapoptosis, likely through decreasing protein levels of its targets, SIRT1, MET, and KLF4. Based on literature reports of SIRT1 activity on FoxO3 and our previous finding of increased nuclear acetylated-FoxO3, we speculate that a miR-34a-mediated decrease in SIRT1 may enhance FoxO3 acetylation levels.