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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 (TGFβ1) 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 TGFβ1 pathway-expressing melanoma cells and that HIF1A upregulates miR-210, miR-218, miR-224, and miR-452. Reduced expression of these four miRNAs in TGFβ1 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 TGFβ1 pathway-expressing melanoma cells, in part via alterations in these four miRNAs.

journal_name

Pigment Cell Melanoma Res

journal_title

Pigment cell & melanoma research

authors

Hwang HW,Baxter LL,Loftus SK,Cronin JC,Trivedi NS,Borate B,Pavan WJ

doi

10.1111/pcmr.12255

subject

Has Abstract

pub_date

2014-09-01 00:00:00

pages

777-87

issue

5

eissn

1755-1471

issn

1755-148X

journal_volume

27

pub_type

杂志文章

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