| RRC ID |
37639
|
| Author |
Coulouarn C, Factor VM, Andersen JB, Durkin ME, Thorgeirsson SS.
|
| Title |
Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties.
|
| Journal |
Oncogene
|
| Abstract |
Growing evidence indicates that microRNAs have a significant role in tumor development and may constitute robust biomarkers for cancer diagnosis and prognosis. In this study, we evaluated the clinical and functional relevance of microRNA-122 (miR-122) expression in human hepatocellular carcinoma (HCC). We report that miR-122 is specifically repressed in a subset of primary tumors that are characterized by poor prognosis. We further show that the loss of miR-122 expression in tumor cells segregates with specific gene expression profiles linked to cancer progression, namely the suppression of hepatic phenotype and the acquisition of invasive properties. We identify liver-enriched transcription factors as central regulatory molecules in the gene networks associated with loss of miR-122, and provide evidence suggesting that miR-122 is under the transcriptional control of HNF1A, HNF3A and HNF3B. We further show that loss of miR-122 results in an increase of cell migration and invasion and that restoration of miR-122 reverses this phenotype. In conclusion, miR-122 is a marker of hepatocyte-specific differentiation and an important determinant in the control of cell migration and invasion. From a clinical point of view, our study emphasizes miR-122 as a diagnostic and prognostic marker for HCC progression.
|
| Volume |
28(40)
|
| Pages |
3526-36
|
| Published |
2009-10-8
|
| DOI |
10.1038/onc.2009.211
|
| PII |
onc2009211
|
| PMID |
19617899
|
| PMC |
PMC3492882
|
| MeSH |
Carcinoma, Hepatocellular / genetics*
Carcinoma, Hepatocellular / mortality
Carcinoma, Hepatocellular / pathology
Cell Line, Tumor
Gene Expression Profiling
Humans
Liver Neoplasms / genetics*
Liver Neoplasms / mortality
Liver Neoplasms / pathology
MicroRNAs / analysis
MicroRNAs / physiology*
Neoplasm Invasiveness
Neoplasm Metastasis
Phenotype
Prognosis
|
| IF |
7.971
|
| Times Cited |
482
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
ONCOLOGY
GENETICS & HEREDITY
CELL BIOLOGY
|
| Resource |
| Human and Animal Cells |
HuH-6(RCB1367) |
