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MicroRNA-21 is overexpressed in human cholangiocarcinoma and regulates programmed cell death 4 and tissue inhibitor of metalloproteinase 3.
- Source :
-
Hepatology (Baltimore, Md.) [Hepatology] 2009 May; Vol. 49 (5), pp. 1595-601. - Publication Year :
- 2009
-
Abstract
- Unlabelled: Cholangiocarcinomas (CCAs) are aggressive cancers, with high mortality and poor survival rates. Only radical surgery offers patients some hope of cure; however, most patients are not surgical candidates because of late diagnosis secondary to relatively poor accuracy of diagnostic means. MicroRNAs (miRs) are involved in every cancer examined, but they have not been evaluated in primary CCA. In this study, miR arrays were performed on five primary CCAs and five normal bile duct specimens (NBDs). Several miRs were dysregulated and miR-21 was overexpressed in CCAs. miR-21 differential expression in these 10 specimens was verified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). To validate these findings, qRT-PCR for miR-21 was then performed on 18 additional primary CCAs and 12 normal liver specimens. MiR-21 was 95% sensitive and 100% specific in distinguishing between CCA and normal tissues, with an area under the receiver operating characteristic curve of 0.995. Inhibitors of miR-21 increased protein levels of programmed cell death 4 (PDCD4) and tissue inhibitor of metalloproteinases 3 (TIMP3). Notably, messenger RNA levels of TIMP3 were significantly lower in CCAs than in normals.<br />Conclusions: MiR-21 is overexpressed in human CCAs. Furthermore, miR-21 may be oncogenic, at least in part, by inhibiting PDCD4 and TIMP3. Finally, these data suggest that TIMP3 is a candidate tumor suppressor gene in the biliary tree.
- Subjects :
- Adult
Aged
Aged, 80 and over
Cell Line, Tumor
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Male
Middle Aged
Oligonucleotide Array Sequence Analysis
RNA, Messenger metabolism
Reverse Transcriptase Polymerase Chain Reaction
Apoptosis Regulatory Proteins metabolism
Bile Duct Neoplasms metabolism
Bile Ducts, Intrahepatic metabolism
Cholangiocarcinoma metabolism
MicroRNAs metabolism
RNA-Binding Proteins metabolism
Tissue Inhibitor of Metalloproteinase-3 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1527-3350
- Volume :
- 49
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Hepatology (Baltimore, Md.)
- Publication Type :
- Academic Journal
- Accession number :
- 19296468
- Full Text :
- https://doi.org/10.1002/hep.22838