The precise functions and mechanisms of microRNAs (miR) in gallbladder cancer (GBC) remain elusive. In this study, we found that miR-135a-5p expression is often dampened and correlated with neoplasm histologic grade in GBC. MicroRNA-135a-5p introduction clearly inhibited GBC cell proliferation in vitro and in vivo. Moreover, very low density lipoprotein receptor (VLDLR), which is often upregulated in GBC tissues, was identified as a direct functional target of miR-135a-5p. Furthermore, the p38 MAPK pathway was proven to be involved in miR-135a-VLDLR downstream signaling. Together, these results suggested that the miR-135a–VLDLR–p38 axis may contribute to GBC cell proliferation.

Gallstone disease is a common and frequently occurring disease in human, and it is the main disease among the digestive system diseases. The incidence of gallstone disease in western countries is about 5%-22%, and common bile duct stones (CBDS) accounts for 8%-20%. CBDS easily lead to biliary obstruction, secondary cholangitis, pancreatitis, and obstructive jaundice, even endanger life. Therefore, it needs timely treatment once diagnosed. The recurrence of choledocholithiasis after bile duct stones clearance involves complicated factors and cannot be completely elaborated by a single factor. The risk factors for recurrence of choledocholithiasis include bacteria, biliary structure, endoscopic and surgical treatment, and inflammation. The modalities for management of choledocholithiasis are endoscopic retrograde cholangiopancreatography (ERCP), laparoscopic or open common bile duct exploration, dissolving solutions, extracorporeal shockwave lithotripsy (ESWL), percutaneous radiological interventions, electrohydraulic lithotripsy (EHL) and laser lithotripsy. We compare the different benefits between surgery and ERCP. And finally, we make a summary of the current strategy for reducing the recurrence of CBDS and future perspectives for CBDS management.

Gallbladder cancer (GBC) is an aggressive disease in which epithelial-mesenchymal transition (EMT) plays a critical role. Whether inhibition of mTOR effects via EMT reversal in GBC remains unclear. Using genetic and pharmacologic inhibitions of mTOR, we investigated the changes of EMT levels in GBC cells. Expressions of EMT related genes were also studied. Migration and invasion assays were carried out and in vivo tumour metastasis mouse models were established. Circulating tumour DNA was quantified. We used EMT index (ratio of Vimentin/Ecadherin expression) to profile EMT levels. We found that inhibition of mTOR using shRNAs and rapamycin inhibited EMT in GBC-SD gallbladder cancer cells. Inhibition of mTOR inhibited EMT in GBC-SD cells in TGF-β-dependent manner, which was contributed majorly by mTORC2 inhibition. Rapamycin decreased invasiveness and migration of GBC-SD cells in vitro and in vivo. We have in the current study shown that rapamycin diminishes the ability of invasion and migration of GBC via inhibition of TGF-β-dependent EMT. Our findings contribute to the understanding of the carcinogenesis of GBC.