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Distinct microRNA expression signatures are associated with melanoma subtypes and are regulated by HIF1A.


ABSTRACT: The complex genetic changes underlying metastatic melanoma need to be deciphered to develop new and effective therapeutics. Previously, genome-wide microarray analyses of human melanoma identified two reciprocal gene expression programs, including transcripts regulated by either transforming growth factor, beta 1 (TGF?1) pathways, or microphthalmia-associated transcription factor (MITF)/SRY-box containing gene 10 (SOX10) pathways. We extended this knowledge by discovering that melanoma cell lines with these two expression programs exhibit distinctive microRNA (miRNA) expression patterns. We also demonstrated that hypoxia-inducible factor 1 alpha (HIF1A) is increased in TGF?1 pathway-expressing melanoma cells and that HIF1A upregulates miR-210, miR-218, miR-224, and miR-452. Reduced expression of these four miRNAs in TGF?1 pathway-expressing melanoma cells arrests the cell cycle, while their overexpression in mouse melanoma cells increases the expression of the hypoxic response gene Bnip3. Taken together, these data suggest that HIF1A may regulate some of the gene expression and biological behavior of TGF?1 pathway-expressing melanoma cells, in part via alterations in these four miRNAs.

SUBMITTER: Hwang HW 

PROVIDER: S-EPMC4150815 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Distinct microRNA expression signatures are associated with melanoma subtypes and are regulated by HIF1A.

Hwang Hun-Way HW   Baxter Laura L LL   Loftus Stacie K SK   Cronin Julia C JC   Trivedi Niraj S NS   Borate Bhavesh B   Pavan William J WJ  

Pigment cell & melanoma research 20140527 5


The complex genetic changes underlying metastatic melanoma need to be deciphered to develop new and effective therapeutics. Previously, genome-wide microarray analyses of human melanoma identified two reciprocal gene expression programs, including transcripts regulated by either transforming growth factor, beta 1 (TGFβ1) pathways, or microphthalmia-associated transcription factor (MITF)/SRY-box containing gene 10 (SOX10) pathways. We extended this knowledge by discovering that melanoma cell line  ...[more]

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