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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 10, 2016 |
| Title |
microRNA-7-5p inhibits melanoma cell proliferation and metastasis by suppressing RelA |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
microRNA-7-5p (miR-7-5p) is an established tumor suppressor in multiple cancer types and inhibits growth and invasion by suppressing expression and activity of the epidermal growth factor receptor (EGFR) signaling pathway. While melanoma is not typically driven by EGFR signaling, expression of miR-7-5p is reduced in metastatic tumors compared to primary melanoma. Here, we investigated the biological and clinical significance of miR-7-5p in melanoma. Our results showed that augmenting miR-7-5p expression in vitro markedly reduced tumor cell viability, colony formation and induced cell cycle arrest. Furthermore, ectopic expression of miR-7-5p reduced migration and invasion of melanoma cells in vitro and reduced melanoma lung colonizationmetastasis in vivo. To investigate the mechanism underlying this effect, we used cDNA microarray analysis to identify a subset of putative miR-7-5p target genes associated with melanoma and metastasis. Of these, we confirmed nuclear factor kappa B (NF-κB) subunit RelA, as a novel direct target of miR-7-5p in melanoma cells, such that miR-7-5p suppresses NF-κB activity to decrease expression of canonical NF-κB target genes, including IL-1a, IL-6 and IL-8. Importantly, the effects of miR-7-5p on melanoma cell growth, cell cycle, migration and invasion were recapitulated by RelA knockdown. Finally, analysis of gene array datasets from multiple melanoma patient cohorts revealed an association between elevated RelA expression and poor survival, further emphasizing the clinical significance of RelA and its downstream signaling effectors.. Taken together, our data suggest that miR-7-5p replacement therapy might have clinical utility in melanoma to inhibit the metastatic process, in part through its inactivation of RelA/NF-kB signaling.
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| Overall design |
Total RNA was extracted from WM266-4 cells transfected with miR-NC or miR-7-5p precursor molecules (30 nM) for 24 h, using Qiazol reagent (Qiagen).
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| Web link |
http://www.ncbi.nlm.nih.gov/pubmed/27203220
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| Contributor(s) |
Candy PA |
| Citation(s) |
27203220 |
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| Submission date |
Jan 25, 2016 |
| Last update date |
Aug 13, 2018 |
| Contact name |
Patrick Aaron Candy |
| E-mail(s) |
[email protected]
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| Organization name |
Perkins Institute
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| Department |
Cancer Medicine
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| Street address |
6 Verdun St
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| City |
Nedlands |
| State/province |
Western Australia |
| ZIP/Postal code |
6009 |
| Country |
Australia |
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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 |
PRJNA309691 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE77196_RAW.tar |
26.2 Mb |
(http)(custom) |
TAR |
| GSE77196_non-normalized.txt.gz |
3.5 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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