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| Status |
Public on Jun 10, 2017 |
| Title |
Gene and microRNA modulation upon ET-743 treatment in a human intrahepatic cholangiocarcinoma paired patient derived xenograft and cell line [miRNA expression] |
| Organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by array
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| Summary |
Transcriptional profiling and microRNA profiling of paired PDX and derived cell line MT-CHC01 upon ET-743 treatement
Intrahepatic cholangiocarcinoma (ICC) is an aggressive and lethal malignancy with limited therapeutic options. ET-743 has a high antitumor activity in preclinical models of biliary tract carcinoma (BTC), being a promising alternative treatment. Here, we studied the effect of ET-743 at transcriptomic level on an ICC patient derived xenograft (PDX) and on the derived cell line, MT-CHC01. Further, putative targets of ET-743 were explored in the in vitro model. In vitro, ET-743 inhibited genes involved in protein modification, neurogenesis, migration, and motility; it induced the expression of genes involved in keratinization, tissues development, and apoptotic processes. In the PDX model, ET-743 affected ECM-receptor interaction, focal adhesion, complement and coagulation cascades, Hedgehog, MAPK, EGFR signaling via PIP3 pathway, and apoptosis. In MT-CHC01, 24 microRNAs were deregulated upon drug treatment. Only 5 microRNAs were perturbed by ET-743 in PDX; 2 up and 3 down-regulated. Among down- regulated genes, we selected SYK and LGALS1; their silencing caused a significantly reduction of migration, but did not affect proliferation in MT-CHC01 and WITT cells. In conclusion, we described that ET-743 affected genes and microRNAs involved in tumor progression and metastatic processes, reflecting data previously obtained at macroscopically level; in particular, we identified SYK and LGALS1 as new putative targets of ET-743.
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| Overall design |
MicroRNA alterations upon ET-743 treatement
MT-CHC01 cell line treated with ET-743 at the dose of 5 nM for 24 hours vs MT-CHC01 cell line untreated;ICC PDX treated with ET-743 at the dose of 0.15 mg/Kg/weekly for three weeks vs ICC PDX untreated
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| Contributor(s) |
Neia CP, cavalloni G, Chiorino G, Ostano P, Leone F, Aglietta M |
| Citation(s) |
27902465 |
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| Submission date |
Jul 28, 2016 |
| Last update date |
Jun 10, 2017 |
| Contact name |
giovanna chiorino |
| E-mail(s) |
giovanna.chiorino@gmail.com
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| Organization name |
Fondo Edo Tempia
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| Department |
Cancer Genomics
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| Street address |
via malta 3
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| City |
Biella |
| ZIP/Postal code |
13900 |
| Country |
Italy |
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| Platforms (1) |
| GPL15159 |
Agilent-031181 Unrestricted_Human_miRNA_V16.0_Microarray 030840 (Probe Name version) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE84939 |
Gene and microRNA modulation upon ET-743 treatment in a human intrahepatic cholangiocarcinoma paired patient derived xenograft and cell line |
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| Relations |
| BioProject |
PRJNA335715 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE84938_RAW.tar |
62.8 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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