MicroRNA-26a is strongly downregulated in melanoma and induces cell death through repression of silencer of death domains (SODD)

Steven N. Reuland, Shilo M. Smith, Lynne T. Bemis, Nathaniel B. Goldstein, Adam R. Almeida, Katie A. Partyka, Victor E. Marquez, Qinghong Zhang, David A. Norris, Yiqun G. Shellman

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Abstract

Melanoma is an aggressive cancer that metastasizes rapidly and is refractory to conventional chemotherapies. Identifying microRNAs (miRNAs) that are responsible for this pathogenesis is therefore a promising means of developing new therapies. We identified miR-26a through microarray and quantitative reverse-transcription-PCR (qRT-PCR) experiments as an miRNA that is strongly downregulated in melanoma cell lines as compared with primary melanocytes. Treatment of cell lines with miR-26a mimic caused significant and rapid cell death compared with a negative control in most melanoma cell lines tested. In surveying targets of miR-26a, we found that protein levels of SMAD1 (mothers against decapentaplegic homolog 1) and BAG-4/SODD were strongly decreased in sensitive cells treated with miR-26a mimic as compared with the control. The luciferase reporter assays further demonstrated that miR-26a can repress gene expression through the binding site in the 3′ untranslated region (3′UTR) of SODD (silencer of death domains). Knockdown of these proteins with small interfering RNA (siRNA) showed that SODD has an important role in protecting melanoma cells from apoptosis in most cell lines sensitive to miR-26a, whereas SMAD1 may have a minor role. Furthermore, transfecting cells with a miR-26a inhibitor increased SODD expression. Our findings indicate that miR-26a replacement is a potential therapeutic strategy for metastatic melanoma, and that SODD, in particular, is a potentially useful therapeutic target.

Original languageEnglish (US)
Pages (from-to)1286-1293
Number of pages8
JournalJournal of Investigative Dermatology
Volume133
Issue number5
DOIs
StatePublished - May 2013

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Cell death
MicroRNAs
Melanoma
Cell Death
Down-Regulation
Cells
Cell Line
Smad Proteins
Chemotherapy
Surveying
3' Untranslated Regions
Transcription
Microarrays
Luciferases
Gene expression
Refractory materials
Small Interfering RNA
Melanocytes
Assays
Therapeutics

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MicroRNA-26a is strongly downregulated in melanoma and induces cell death through repression of silencer of death domains (SODD). / Reuland, Steven N.; Smith, Shilo M.; Bemis, Lynne T.; Goldstein, Nathaniel B.; Almeida, Adam R.; Partyka, Katie A.; Marquez, Victor E.; Zhang, Qinghong; Norris, David A.; Shellman, Yiqun G.

In: Journal of Investigative Dermatology, Vol. 133, No. 5, 05.2013, p. 1286-1293.

Research output: Contribution to journalArticle

Reuland, SN, Smith, SM, Bemis, LT, Goldstein, NB, Almeida, AR, Partyka, KA, Marquez, VE, Zhang, Q, Norris, DA & Shellman, YG 2013, 'MicroRNA-26a is strongly downregulated in melanoma and induces cell death through repression of silencer of death domains (SODD)', Journal of Investigative Dermatology, vol. 133, no. 5, pp. 1286-1293. https://doi.org/10.1038/jid.2012.400
Reuland, Steven N. ; Smith, Shilo M. ; Bemis, Lynne T. ; Goldstein, Nathaniel B. ; Almeida, Adam R. ; Partyka, Katie A. ; Marquez, Victor E. ; Zhang, Qinghong ; Norris, David A. ; Shellman, Yiqun G. / MicroRNA-26a is strongly downregulated in melanoma and induces cell death through repression of silencer of death domains (SODD). In: Journal of Investigative Dermatology. 2013 ; Vol. 133, No. 5. pp. 1286-1293.
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