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Distinct micro RNA expression signatures are associated with melanoma subtypes and are regulated by HIF 1A
Author(s) -
Hwang HunWay,
Baxter Laura L.,
Loftus Stacie K.,
Cronin Julia C.,
Trivedi Niraj S.,
Borate Bhavesh,
Pavan William J.
Publication year - 2014
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12255
Subject(s) - microphthalmia associated transcription factor , hif1a , sox10 , microrna , biology , melanoma , transcription factor , gene expression , cancer research , gene expression profiling , regulation of gene expression , transforming growth factor beta , gene , signal transduction , microbiology and biotechnology , genetics
Summary 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 β 1) pathways, or microphthalmia‐associated transcription factor ( MITF )/ SRY ‐box containing gene 10 ( SOX 10) pathways. We extended this knowledge by discovering that melanoma cell lines with these two expression programs exhibit distinctive micro RNA (mi RNA ) expression patterns. We also demonstrated that hypoxia‐inducible factor 1 alpha ( HIF 1A) is increased in TGF β 1 pathway‐expressing melanoma cells and that HIF 1A upregulates miR‐210, miR‐218, miR‐224, and miR‐452. Reduced expression of these four mi RNA s in TGF β 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 HIF 1A may regulate some of the gene expression and biological behavior of TGF β 1 pathway‐expressing melanoma cells, in part via alterations in these four mi RNA s.