MicroRNAs in biliary diseases

Table 1 Classification of miRNAs differentially expressed in cholangiocarcinoma regarding their action, expression and targets

miRNA	Expression	Disease	Target	Altered function	Ref.
miR-320	Down	Human-ICC	Mcl-1		[17]
miR-29b	Down	Human-CCA	Mcl-1		[21,30]
miR-204	Down	Human-ICC	Bcl-2	Apoptosis	[17]
miR-25	Up	Human-ICC	DR4		[29]
miR-21	Up	Human-CCA	PDCD4		[20,25]
miR-421	Up	Human-ICC	FXR		[22]
miR-34a	Down	Mouse-CCA	c-Myc		[27]
miR-210	Up	Mouse-CCA	Mnt	Proliferation	[27]
miR-21	Up	Human-CCA	PTEN		[18,21,25]
miR-26a	Up	Human-CCA	GSK-3β		[26]
miR-421	Up	Human-ICC	FXR		[22]
miR-21	Up	Human-CCA	TIMP-3	Migration	[20]
miR-26a	Up	Human-CCA	GSK-3β		[26]
miR-494	Down	Human-CCA	CDK-6	Cell cycle	[19]
miR-141	Up	Human-CCA	Gen CLOCK	Circadian rhythm	[18]
miR-370	Down	Human-CCA	MAP3K8, DNMT-1		[38]
miR-373	Down	Human-ECC	MBD2	Epigenetics	[36,37]
miR-148a	Down	Human-CCA	DNMT-1		[39]
miR-152	Down	Human-CCA	DNMT-1		[39]
miR-let7a	Up	Human-CCA	NF2		[41]
miR-21	Up	Human-CCA	PTEN	Chemoresistance	[18]
miR-200b	Up	Human-CCA	PTPN12		[18]

miRNA-15a/Cdc25A interplay participates in hepatic cystogenesis of polycystic liver diseases. miRNA-15a directly targets the cell cycle regulator Cdc25a. In polycystic rat and human cholangiocytes, miR15a is downregulated, thus resulting in Cdc25a upregulation, cell proliferation and cystogenesis. The Cdc25a inhibitor vitamin K3 was demonstrated to target Cdc25a, blocking the hepatorenal cystogenesis of several rodent models of polycystic kidney and liver disease. This suggests the therapeutic potential of vitamin K3 for polycystic kidney and liver diseases. CCA: Cholangiocarcinoma; ICC: Intrahepatic cholangiocarcinoma; ECC: Extrahepatic cholangiocarcinoma; CDK: Cell division kinase; Mcl-1: Myeloid cell leukemia sequence 1; Bcl-2: B-cell lymphoma 2; CDK: Cyclin-dependent kinase; DR4: Death receptor 4; PDCD4: Programmed cell death protein 4; FXR: Farnesoid X receptor; TIMP: Tissue inhibitor of metalloproteinase; GSK: Glycogen synthase kinase; MBD: Methyl-CpG-binding domain; MAP3K8: Mitogen-activated protein kinase 8; DNMT: DNA methyltransferases; NF2: Neurofibromatosis 2; PTEN: Phosphatase and tension homolog; PTPN12: Protein tyrosine phosphatase non-receptor type 12.