| RRC ID |
64109
|
| 著者 |
Letelier P, García P, Leal P, Álvarez H, Ili C, López J, Castillo J, Brebi P, Roa JC.
|
| タイトル |
miR-1 and miR-145 act as tumor suppressor microRNAs in gallbladder cancer.
|
| ジャーナル |
Int J Clin Exp Pathol
|
| Abstract |
The development of miRNA-based therapeutics represents a new strategy in cancer treatment. The objectives of this study were to evaluate the differential expression of microRNAs in gallbladder cancer (GBC) and to assess the functional role of miR-1 and miR-145 in GBC cell behavior. A profile of miRNA expression was determined using DharmaconTM microarray technology. Differential expression of five microRNAs was validated by TaqMan reverse transcription quantitative-PCR in a separate cohort of 8 tumors and 3 non-cancerous samples. Then, we explored the functional role of miR-1 and miR-145 in tumor cell behavior by ectopic in vitro expression in the GBC NOZ cell line. Several miRNAs were found to be aberrantly expressed in GBC; most of these showed a significantly decreased expression compared to non-neoplastic tissues (Q value<0.05). The differential expression of 7 selected miRNAs was confirmed by real time PCR. Pathway enrichment analysis revealed that the most deregulated miRNAs (miR-1, miR-133, miR-143 and miR-145) collectively targeted a number of genes belonging to signaling pathways such as TGF-β, ErbB3, WNT and VEGF, and those regulating cell motility or adhesion. The ectopic expression of miR-1 and miR-145 in NOZ cells significantly inhibited cell viability and colony formation (P<0.01) and reduced gene expression of VEGF-A and AXL. This study represents the first investigation of the miRNA expression profile in gallbladder cancer, and our findings showed that several miRNAs are deregulated in this neoplasm. In vitro functional assays suggest that miR-1 and miR-145 act as tumor suppressor microRNAs in GBC.
|
| 巻・号 |
7(5)
|
| ページ |
1849-67
|
| 公開日 |
2014-1-1
|
| PMID |
24966896
|
| PMC |
PMC4069933
|
| MeSH |
Axl Receptor Tyrosine Kinase
Cell Line, Tumor
Cell Proliferation / genetics
Cell Survival / genetics
Cluster Analysis
Gallbladder Neoplasms / genetics*
Gallbladder Neoplasms / metabolism
Gene Expression Profiling / methods
Gene Expression Regulation, Neoplastic*
Gene Regulatory Networks
Humans
MicroRNAs / genetics*
MicroRNAs / metabolism
Oligonucleotide Array Sequence Analysis
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins / metabolism
Real-Time Polymerase Chain Reaction
Receptor Protein-Tyrosine Kinases / genetics
Receptor Protein-Tyrosine Kinases / metabolism
Reproducibility of Results
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / genetics
Time Factors
Transfection
Vascular Endothelial Growth Factor A / genetics
Vascular Endothelial Growth Factor A / metabolism
|
| IF |
0.252
|
| リソース情報 |
| ヒト・動物細胞 |
TGBC14TKB(RCB1186)
TGBC24TKB(RCB1196)
TGBC1TKB(RCB1129)
TGBC2TKB(RCB1130) |
