Detail
Experiment ID:
EXP00488
Reference:
- Title: Profiling of gallbladder carcinoma reveals distinct miRNA profiles and activation of STAT1 by the tumor suppressive miRNA-145-5p.
- Author: Goeppert B, Truckenmueller F, Ori A, Fritz V, Albrecht T, Fraas A, Scherer D, Silos RG, Sticht C, Gretz N, Mehrabi A, Bewerunge-Hudler M, Pusch S, Bermejo JL, Dietrich P, Schirmacher P, Renner M, Roessler S
- Journal: Scientific reports.2019 03 18;9(1):4796.doi:10.1038/s41598-019-40857-3.
- Abstract: Gallbladder carcinoma (GBC) is a biliary tract cancer with few treatment options and poor prognosis. Radical surgery is the only potentially curative treatment option but most patients diagnosed with GBC are unresectable. Thus, there is a great need for the development of new treatment options including targeted therapy. Here, we aimed at identifying deregulated miRNAs and affected pathways involved in GBC development and progression. We performed global miRNA profiling of 40 GBC and 8 normal gallbladder tissues and identified large differences with 30% of miRNAs being differentially expressed (false discovery rate: FDR < 0.001). We found 24 miRNAs to be differentially regulated in GBC with poor outcome (p < 0.05) of which miR-145-5p was the most downregulated miRNA. Overexpression of miR-145-5p significantly reduced cell proliferation and colony formation. Gene expression analysis of cells expressing miR-145-5p mimics revealed activation of the Signal transducer and activator of transcription 1 (STAT1) signaling pathway which is mainly tumor suppressive. Furthermore, the activation of STAT1 by miR-145-5p was specifically observed in gallbladder carcinoma and cholangiocarcinoma but not in hepatocellular carcinoma cells. The Protein Tyrosine Phosphatase Receptor Type F (PTPRF) is downregulated upon miR-145 expression and may be involved in STAT1 regulation. In addition, we found that the STAT1-regulated protein IRF7 is downregulated in GBC compared to normal gallbladder tissue and low IRF7 expression is associated with significantly lower overall survival of GBC patients. Thus, this study identified GBC patient subgroups and provides new mechanistic insights in the tumor suppressive function of miR-145-5p leading to activation of STAT1 signaling.
- PMID: 30886199
Expression Profile:
- Description:MiRNA profiling in gallbladder carcinoma
- Organism:Homo sapiens
- Source:GEO
- Source ID:GSE104165
- Platform: GPL18402
- Number of samples:48
- Overall design:To study the expression profiles of miRNAs in gallbladder carcinoma
- Instrument:Agilent-046064 Unrestricted_Human_miRNA_V19.0_Microarray (miRNA ID version)
Design and Sample:
- Cancer Type:gallbladder carcinoma
- Cancer SubType:N/A
- Cell Line:N/A
- Experimental Design:cancer vs normal
- Case Sample:gallbladder carcinoma
- Control Sample:normal gallbladder
- Num of Case:40
- Num of Control:8
- Quantification Software:Limma
- Num of miRNAs:2006
Identification:
- Num of Up:581
- Num of Down:389
Time Info:
- Create Time2021-06-04
- Update Time:2021-06-07
Status:
| miRNA ID | Cancer Type | Design | logFC | AveExpr | T value | P value | adj Pvalue | Status | Plot |
|---|