microRNA-7-5p inhibits melanoma cell proliferation and metastasis by suppressing RelA/NF-κB

Giles, Keith M., Brown, Rikki A. M., Ganda, Clarissa, Podgorny, Melissa J., Candy, Patrick A., Wintle, Larissa C., Richardson, Kirsty L., Kalinowski, Felicity C., Stuart, Lisa M., Epis, Michael R., Haass, Nikolas K., Herlyn, Meenhard and Leedman, Peter J. (2016) microRNA-7-5p inhibits melanoma cell proliferation and metastasis by suppressing RelA/NF-κB. Oncotarget, 7 22: 31663-31680. doi:10.18632/oncotarget.9421

Author Giles, Keith M.
Brown, Rikki A. M.
Ganda, Clarissa
Podgorny, Melissa J.
Candy, Patrick A.
Wintle, Larissa C.
Richardson, Kirsty L.
Kalinowski, Felicity C.
Stuart, Lisa M.
Epis, Michael R.
Haass, Nikolas K.
Herlyn, Meenhard
Leedman, Peter J.
Title microRNA-7-5p inhibits melanoma cell proliferation and metastasis by suppressing RelA/NF-κB
Journal name Oncotarget   Check publisher's open access policy
ISSN 1949-2553
Publication date 2016-05-31
Year available 2016
Sub-type Article (original research)
DOI 10.18632/oncotarget.9421
Open Access Status DOI
Volume 7
Issue 22
Start page 31663
End page 31680
Total pages 18
Place of publication Albany, NY United States
Publisher Impact Journals
Language eng
Formatted abstract
microRNA-7-5p (miR-7-5p) is a 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 EGFR-driven, 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. We found 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 metastasis in vivo. 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-1β, 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 show that miR-7-5p is a potent inhibitor of melanoma growth and metastasis, in part through its inactivation of RelA/NF-κB signaling. Furthermore, miR-7-5p replacement therapy could have a role in the treatment of this disease.
Keyword MicroRNA
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 4 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 24 Jun 2016, 03:19:23 EST by Nikolas Haass on behalf of UQ Diamantina Institute