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| Status |
Public on Apr 21, 2018 |
| Title |
MicroRNA-590-3p promotes ovarian cancer growth and metastasis via a novel FOXA2-Versican pathway |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Epithelial ovarian cancer (EOC) is the deadliest gynecological cancer. MicroRNAs (miRNAs) are small non-coding RNAs that play important roles in gene regulation and their dysregulation is associated with many diseases. In this study, we determined the expression and function of miR-590-3p in EOC. We found that miR-590-3p levels were higher in high-grade carcinoma when compared to low-grade or tumours with low malignant potential. Interestingly, plasma levels of miR-590-3p were significantly higher in EOC patients than in subjects with benign gynaecological disorders. Transient transfection of miR-590-3p mimics, or stable transfection of mir-590, increased cell growth, migration, and invasion. In vivo studies revealed that mir-590 accelerated tumour growth and metastasis. Using a cDNA microarray, we identified Forkhead box A2 (FOXA2) and Versican (VCAN) as a top downregulated and a top upregulated gene, respectively, by mir-590. We showed that miR-590-3p targeted FOXA2 3’ UTR to suppress its expression. In addition, knockdown of FOXA2 by siRNAs or knockout of FOXA2 by CRISPR/Cas9 enhanced cell proliferation, migration, and invasion. Overexpression of FOXA2 decreased, while knockout of FOXA2 increased, VCAN mRNA and protein levels and ChIP-qPCR revealed that FOXA2 binds to VCAN promoter. Interrogation of the TCGA ovarian cancer database revealed a negative relationship between FOXA2 and VCAN mRNA levels in EOC tumours and that high FOXA2/low VCAN mRNA levels in tumours were positively correlated with patient survival. Finally, overexpression of FOXA2 or silencing of VCAN reversed the effects of mir-590. These findings demonstrate that miR-590-3p promotes EOC development via a novel FOXA2-VCAN pathway.
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| Overall design |
A total of 6 samples were analyzed. Three control (EV) and three mir-590 overexpressing samples
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| Contributor(s) |
Salem M, Peng C |
| Citation(s) |
29748371 |
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| Submission date |
Apr 20, 2018 |
| Last update date |
Aug 13, 2018 |
| Contact name |
Chun Peng |
| E-mail(s) |
[email protected]
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| Organization name |
York University
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| Department |
Biology
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| Street address |
4700 Keele Street, North York, ON, Canada
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| City |
Toronto |
| State/province |
Ontario |
| ZIP/Postal code |
M3J 1P3 |
| Country |
Canada |
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| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA451190 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE113440_RAW.tar |
35.8 Mb |
(http)(custom) |
TAR (of IDAT) |
| GSE113440_non-normalized.txt.gz |
1.4 Mb |
(ftp)(http) |
TXT |
| GSE113440_normalized.txt.gz |
2.2 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
| Processed data are available on Series record |
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