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microRNA-155, induced by interleukin-1ß, represses the expression of microphthalmia-associated transcription factor (MITF-M) in melanoma cells.

Arts N, Cané S, Hennequart M, Lamy J, Bommer G, Van den Eynde B, De Plaen E - PLoS ONE (2015)

Bottom Line: We previously reported that interleukin-1ß (IL-1ß) can downregulate MITF-M levels.Notably, we also observed a strong negative correlation between MITF-M and miR-155 levels in a mouse model of melanoma.Taken together, our results indicate that MITF-M downregulation by inflammatory stimuli might be partly due to miR-155 upregulation.

View Article: PubMed Central - PubMed

Affiliation: Ludwig Institute for Cancer Research, Brussels and Université Catholique de Louvain, Brussels, Belgium.

ABSTRACT
Loss of expression of surface antigens represents a significant problem for cancer immunotherapy. Microphthalmia-associated transcription factor (MITF-M) regulates melanocyte fate by driving expression of many differentiation genes, whose protein products can be recognized by cytolytic T lymphocytes. We previously reported that interleukin-1ß (IL-1ß) can downregulate MITF-M levels. Here we show that downregulation of MITF-M expression by IL-1ß was paralleled by an upregulation of miR-155 expression in four melanoma lines. We confirmed that miR-155 was able to target endogenous MITF-M in melanoma cells and demonstrated a role for miR-155 in the IL-1ß-induced repression of MITF-M by using an antagomiR. Notably, we also observed a strong negative correlation between MITF-M and miR-155 levels in a mouse model of melanoma. Taken together, our results indicate that MITF-M downregulation by inflammatory stimuli might be partly due to miR-155 upregulation. This could represent a novel mechanism of melanoma immune escape in an inflammatory microenvironment.

No MeSH data available.


Related in: MedlinePlus

IL-1ß downregulates the expression of MITF-M and upregulates the expression of miR-155 in 2 melanoma cell lines.(A) Expression of MITF-M was analyzed by quantitative RT-PCR in melanoma cell lines LB2201-MEL and LB2259-MEL incubated with IL-1ß (10 ng/ml) for 4h or 24h. The result was normalized to ß-actin expression (means ± SD for 3 or 4 independent experiments, respectively). (B) Expression of miRNAs potentially targeting MITF-M (miR-96, miR-137, miR-148a, miR-155, miR-182 and miR-340) was analyzed by quantitative RT-PCR in the same samples and normalized to RNU44 expression. The table indicates the miRNA fold change when cells were treated with IL-1ß for 4h or 24h.
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pone.0122517.g001: IL-1ß downregulates the expression of MITF-M and upregulates the expression of miR-155 in 2 melanoma cell lines.(A) Expression of MITF-M was analyzed by quantitative RT-PCR in melanoma cell lines LB2201-MEL and LB2259-MEL incubated with IL-1ß (10 ng/ml) for 4h or 24h. The result was normalized to ß-actin expression (means ± SD for 3 or 4 independent experiments, respectively). (B) Expression of miRNAs potentially targeting MITF-M (miR-96, miR-137, miR-148a, miR-155, miR-182 and miR-340) was analyzed by quantitative RT-PCR in the same samples and normalized to RNU44 expression. The table indicates the miRNA fold change when cells were treated with IL-1ß for 4h or 24h.

Mentions: When analyzing the expression of MITF-M in two melanoma cell lines, LB2201-MEL and LB2259-MEL, we observed a significant downregulation of the expression of MITF-M mRNA after incubation with IL-1ß for 4h and 24h, consistent with a previous study from our laboratory (Fig 1A) [19]. This could be due either to reduced production (e.g. via repression of MITF-M transcription) or to destabilization of the MITF-M mRNA.


microRNA-155, induced by interleukin-1ß, represses the expression of microphthalmia-associated transcription factor (MITF-M) in melanoma cells.

Arts N, Cané S, Hennequart M, Lamy J, Bommer G, Van den Eynde B, De Plaen E - PLoS ONE (2015)

IL-1ß downregulates the expression of MITF-M and upregulates the expression of miR-155 in 2 melanoma cell lines.(A) Expression of MITF-M was analyzed by quantitative RT-PCR in melanoma cell lines LB2201-MEL and LB2259-MEL incubated with IL-1ß (10 ng/ml) for 4h or 24h. The result was normalized to ß-actin expression (means ± SD for 3 or 4 independent experiments, respectively). (B) Expression of miRNAs potentially targeting MITF-M (miR-96, miR-137, miR-148a, miR-155, miR-182 and miR-340) was analyzed by quantitative RT-PCR in the same samples and normalized to RNU44 expression. The table indicates the miRNA fold change when cells were treated with IL-1ß for 4h or 24h.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390329&req=5

pone.0122517.g001: IL-1ß downregulates the expression of MITF-M and upregulates the expression of miR-155 in 2 melanoma cell lines.(A) Expression of MITF-M was analyzed by quantitative RT-PCR in melanoma cell lines LB2201-MEL and LB2259-MEL incubated with IL-1ß (10 ng/ml) for 4h or 24h. The result was normalized to ß-actin expression (means ± SD for 3 or 4 independent experiments, respectively). (B) Expression of miRNAs potentially targeting MITF-M (miR-96, miR-137, miR-148a, miR-155, miR-182 and miR-340) was analyzed by quantitative RT-PCR in the same samples and normalized to RNU44 expression. The table indicates the miRNA fold change when cells were treated with IL-1ß for 4h or 24h.
Mentions: When analyzing the expression of MITF-M in two melanoma cell lines, LB2201-MEL and LB2259-MEL, we observed a significant downregulation of the expression of MITF-M mRNA after incubation with IL-1ß for 4h and 24h, consistent with a previous study from our laboratory (Fig 1A) [19]. This could be due either to reduced production (e.g. via repression of MITF-M transcription) or to destabilization of the MITF-M mRNA.

Bottom Line: We previously reported that interleukin-1ß (IL-1ß) can downregulate MITF-M levels.Notably, we also observed a strong negative correlation between MITF-M and miR-155 levels in a mouse model of melanoma.Taken together, our results indicate that MITF-M downregulation by inflammatory stimuli might be partly due to miR-155 upregulation.

View Article: PubMed Central - PubMed

Affiliation: Ludwig Institute for Cancer Research, Brussels and Université Catholique de Louvain, Brussels, Belgium.

ABSTRACT
Loss of expression of surface antigens represents a significant problem for cancer immunotherapy. Microphthalmia-associated transcription factor (MITF-M) regulates melanocyte fate by driving expression of many differentiation genes, whose protein products can be recognized by cytolytic T lymphocytes. We previously reported that interleukin-1ß (IL-1ß) can downregulate MITF-M levels. Here we show that downregulation of MITF-M expression by IL-1ß was paralleled by an upregulation of miR-155 expression in four melanoma lines. We confirmed that miR-155 was able to target endogenous MITF-M in melanoma cells and demonstrated a role for miR-155 in the IL-1ß-induced repression of MITF-M by using an antagomiR. Notably, we also observed a strong negative correlation between MITF-M and miR-155 levels in a mouse model of melanoma. Taken together, our results indicate that MITF-M downregulation by inflammatory stimuli might be partly due to miR-155 upregulation. This could represent a novel mechanism of melanoma immune escape in an inflammatory microenvironment.

No MeSH data available.


Related in: MedlinePlus