MicroRNA-regulated cancer stemness in the patient-derived xenograft model of human cholangiocarcinoma

Objective:MicroRNAs(miRNAs)are highly conserved 19-25 nucleotide small noncoding RNAs,which are primarily involved in gene silencing.This study aims to characterize the functional roles of microRNA-regulated stemness in patientderived cholangiocarcinoma xenograft tumors.

Functional roles of gut bacteria imbalance in cholangiopathies

Cholangiopathies are caused by bile duct damage or inflammation followed by cholestasis leading to liver fibrosis.Bile duct epithelial cells,cholangiocytes,are a primary target for cholangiopathies.Ductular reaction is often observed in cholangiopathies and the proliferation of cholangiocytes is associated with ductular reaction and liver fibrogenesis.Accumulating evidence suggests that patients with chol-angiopathies have different gut bacterial profiles from healthy individuals,indicating the association between gut microbiota and cholangiopathies.Bile acids are produced by hepatocytes and modified by gut bacteria.Bile acids regulate cholangiocyte proliferation but effects vary depending on the type of bile acids.Recent studies suggest that therapies targeting gut bacteria,such as antibiotics administration and gut bacteria depletion or therapies using gut bacteria-associated bile acids,such as ursodeoxycholic acid(UDCA)administration,may be useful for treatments of cholangiopathies,although data are contro-versial depending on animal models or cohorts.This review summarizes current understandings of functional roles of gut bacterial imbalance and strategies for treatments of cholangiopathies targeting gut bacteria.

Diagnostic and therapeutic potentials of microRNAs in cholangiopathies

Cholangiopathies are a group of rare,devastating diseases that arise from damaged cholangiocytes,the cells that line the intra-and extra-hepatic bile ducts of the biliary epithelium.Cholangiopathies result in significant morbidity and mortality and are a major cause of liver transplantation.A better understanding of the underlying pathogenesis that influences cholangiocyte dysregulation and cholangiopathy progression is necessary,considering the dismal prognosis associated with these diseases.MicroRNAs are a class of small,non-coding RNAs that regulate post-transcriptional mRNA expression of specific genes.The role of microRNAs has expanded to include the initiation and development of many diseases,including cholangiopathies.Understanding microRNA regulation of cholangiopathies may provide diagnostic and therapeutic benefit for these diseases.In this review,the authors primarily focus on studies published within the last five years that help determine the diagnostic and therapeutic potential of microRNAs in cholangiopathies.