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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 22, 2012 |
| Title |
MicroRNA profiling in colorectal cancer highlights miR-1 involvement in MET-dependent proliferation |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
Abstract: Altered expression of microRNAs (miRNAs) is associated with development and progression of various human cancers by regulating the translation of oncogenes and tumor suppressor genes. In colorectal cancer (CRC), these regulators complement the Vogelstein multi-step model of pathogenesis and have the potential of becoming a novel class of tumor biomarkers and therapeutic targets. Using QRT-PCR, we measured the expression of 621 mature miRNAs in 40 CRCs and their paired normal tissues and identified 23 significantly deregulated miRNAs. We subsequently evaluated their association with clinical characteristics of the samples and presence of alterations in the molecular markers of CRC progression. Expression levels of miR-31 were correlated with CA19-9 and miR-18a, miR-21 and miR-31 were associated with mutations in APC gene. To investigate the downstream regulation of the differentially expressed miRNAs identified we integrated putative mRNA target predictions with the results of a meta-analysis of seven public gene expression datasets of normal and tumor samples of CRC patients. Many of the CRC deregulated miRNAs computationally map to targets involved in pathways related to progression. Here one promising candidate pair (miR-1 and MET) was studied and functionally validated. We show that miR-1 can have a tumor suppressor function in CRC by directly down-regulating MET oncogene both at RNA and protein level and that re-expression of miR-1 leads to MET driven reduction of cell proliferation and motility, identifying the miR-1 down-modulation as one of the events that could enhance CRC progression.
Note: Each sample has the following information: Type - tissue type (T : Tumor or N: Normal), Patient - patient identifier, Stage - tumor stage (I - IV), Status - disease status at last check-up (ED: evident disease, NED: non-evident disease), CEA - carcinoembryonic antigen (continuous), CA199 - carbohydrate antigen 19-9 (continuous), APC - mutation status of APC gene (0: wild-type, 1: mutated), KRAS - mutation status of KRAS gene (0: wild-type, 1: mutated), chr18qLOH - LOH status of 18q (0: no LOH, 1: LOH), TP53 - mutation status of TP53 gene (0: wild-type, 1: mutated).
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| Overall design |
Tumor and normal counter-parts of 40 colorectal cancer patients (10 of each Stage I to IV) where profiled using TaqMan(r) Array Human MicroRNA A+B Cards v2.0
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| Contributor(s) |
Reid JF, Sokolova V, Zoni E, Lampis A, Pizzamiglio S, Bertan C, Zanutto S, Camerini T, Gallino G, Verderio P, Leo E, Pilotti S, Pierotti MA, Gariboldi M |
| Citation(s) |
22343615 |
| Submission date |
Apr 04, 2011 |
| Last update date |
Mar 23, 2012 |
| Contact name |
James F Reid |
| E-mail(s) |
james.reid@ifom-ieo-campus.it
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| Organization name |
Fondazione Istituto FIRC di Oncologia Molecolare
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| Department |
Molecular Genetics of Cancer
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| Lab |
Cancer genomics
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| Street address |
Via Adamello, 16
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| City |
Milano |
| ZIP/Postal code |
20139 |
| Country |
Italy |
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| Platforms (2) |
| GPL13328 |
TaqMan(r) Array Human MicroRNA A Cards v2.0 |
| GPL13329 |
TaqMan(r) Array Human MicroRNA B Cards v2.0 |
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| Samples (157)
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| Relations |
| BioProject |
PRJNA139427 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE28364_raw_Ct_values_cardA.txt.gz |
94.5 Kb |
(ftp)(http) |
TXT |
| GSE28364_raw_Ct_values_cardB.txt.gz |
81.9 Kb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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