Genetic and epigenetic changes associated with cholangiocarcinoma: From DNA methylation to microRNAs

Table 1 Summary of genes subject to epigenetic silencing during the course of cholangiocarcinoma tumor progression

Gene	Incidence ofmethylation inCCH (%)	Function	Reference
p16INK4a	14-50	Cell cycle regulator	[26,34,47]
p14ARF	38	Cell cycle regulator	[26]
p15INK4b	12-50	Cell cycle regulator	[26,47]
14-3-3 sigma	59.50	Cell cycle regulator	[34]
Semaphorin3B	100	Tumor suppressor	[24]
p73	36	Tumor suppressor	[26]
RassF1A	26-65	Tumor suppressor	[26,47]
hMLH1	25	DNA mismatch repair	[26]
MGMT	11-33	Methyl transferase	[26,34]
GSTP1	6-34	Inactivation of carcinogens	[26,34]
SOCS-3	ND	Inhibits inflammation	[40]
EGFR	ND	Growth factor	[42]
E-cadherin	43	Cell adhesion	[25,26,34,47]

ND: Not determined.

Table 2 MicroRNAs known to be changed in cholangiocar-cinoma

MicroRNA	Targetgene	Function	Directionchangedin CCH	Reference
miR-141	CLOCK	Circadian rhythm	Increased	[16]
miR-200b	PTPN12	Tumor suppressor	Increased	[16]
miR-21	PTEN	Tumor suppressor	Increased	[16]
miR-29b	Mcl-1	Anti-apoptotic gene	Decreased	[18]
miR-370	MAP3K8	Oncogene	Decreased	[17]
let-7a	NF2	Negative regulator of inflammation	Increased	[22]