The role of microRNA expression pattern in human intrahepatic cholangiocarcinoma.
OBJECTIVE
MicroRNAs are a small non-coding family of genes involved in the regulation of gene expression in a post-transcriptional manner and contribute to cell proliferation, differentiation and apoptosis. Our aims were to identify statistically unique miRNA profiles in human intrahepatic cholangiocarcinoma for diagnosis and investigate their specific involvement in various cell biological processes in cholangiocarcinoma.


METHODS
Laser capture microdissection techniques and TaqMan miRNA assays for mature miRNAs were performed to assess the genomewide expression of miRNAs in 27 human ICCs, 10 normal cholangiocyte cells and 8 normal liver tissues precisely and quantitatively. Two selected miRNAs, mir-204 and mir-320, were introduced into cholangiocarcinoma cell lines to examine their effects on potential target genes, Bcl-2 and Mcl-1, respectively.


RESULTS
A cluster of 38 miRNAs was markedly distinguishable between tumor and normal tissues. At least two distinct clusters of tumor samples could be identified that were associated with the higher or lower expression levels of carbohydrate antigen 19-9. Moreover, the exogenous expression of mir-320 or mir-204 could negatively regulate Mcl-1 or Bcl-2 expression and facilitate chemotherapeutic drug-triggered apoptosis.


CONCLUSIONS
miRNA expression profiles are closely associated with the biological and clinical behavior of ICC. The modulation of aberrantly expressed miRNAs might prove a promising therapeutic strategy.
Chen
Lei
L
International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, 200438 Shanghai, PR China.
Yan
He-Xin
HX
Yang
Wen
W
Hu
Liang
L
Yu
Le-Xin
LX
Liu
Qiong
Q
Li
Liang
L
Huang
Dan-Dan
DD
Ding
Jin
J
Shen
Feng
F
Zhou
Wei-Ping
WP
Wu
Meng-Chao
MC
Wang
Hong-Yang
HY
D001650:Bile Duct Neoplasms / Q000235:genetics*; D001653:Bile Ducts, Intrahepatic; D018395:CA-19-9 Antigen / Q000032:analysis; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000032:analysis*; D042282:Microdissection; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D016133:Polymerase Chain Reaction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis
D018395:CA-19-9 Antigen; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2