Background:Mucin plays anessential role in the intrahepatic stone formation, but the mecha-nism of mucinregulation is unclear.

Objective: To investigate the potential implication of miR-93 and WNT pathway in the regula-tionof intrahepatic bile duct mucin expression.

Methods:Thirty patients with or without intrahepatic bile duct stones are involved; Reverse-transcriptionpolymerase chain reaction was performed to evaluate the expression of MUC3,MUC4,MUC5B, MUC5AC mRNA and miR-93 levels. miR-NC or miR-93 mimics was transfectedintointrahepatic biliary epithelial cells. Then mucins and Wnt pathway proteins were detectedbythe immunoblotting, and the target gene TCF7 were validated using the dual luciferaseassay.?-catenin, wnt4, and mucins were an immunohistochemical stain of the intrahepaticbiliaryepithelial tissues.

Results:The expression levels of MUC3, MUC4, MUC5B, and MUC5AC in patients with intra-hepaticbile duct stones are higher than control, as well as Wnt pathway proteins (especially?-cateninand wnt4). Mucins levels increased in wnt4, wnt5a or SB216763-treated HIBECs, andreducedby miR-93 mimics transfection. miR-93 directly targeted TCF7 and repressed Wnt path-wayprotein expression, which reversed the upregulation of mucin levels induced by wnt4 orwnt5a,but not SB216763.

Conclusion: These results suggest a new potential mechanism in intrahepatic stones, regulatingbymiR-93/TCF7, non-canonical Wnt pathway, and mucins.