Limits...
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

Inverse correlation between the expression of MITF-M and that of miR-155 in melanoma cell lines incubated with IL-1ß.(A) The expression of MITF-M, Tyrosinase and miR-155 was analyzed by quantitative RT-PCR in 8 melanoma cell lines incubated with IL-1ß (10 ng/ml) for 4h or 24h. The results were normalized to ß-actin expression for MITF-M and Tyrosinase and to RNU44 for miR-155 (means ± SD for 3 independent experiments). (B) The expression of MITF-M and Tyrosinase proteins was analyzed by Western Blot in the same samples (1 of 3 independent experiments).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4390329&req=5

pone.0122517.g005: Inverse correlation between the expression of MITF-M and that of miR-155 in melanoma cell lines incubated with IL-1ß.(A) The expression of MITF-M, Tyrosinase and miR-155 was analyzed by quantitative RT-PCR in 8 melanoma cell lines incubated with IL-1ß (10 ng/ml) for 4h or 24h. The results were normalized to ß-actin expression for MITF-M and Tyrosinase and to RNU44 for miR-155 (means ± SD for 3 independent experiments). (B) The expression of MITF-M and Tyrosinase proteins was analyzed by Western Blot in the same samples (1 of 3 independent experiments).

Mentions: In the cell lines that show upregulation of miR-155 by IL-1ß our results suggest that both reduced mRNA transcription and mRNA destabilization occur (S1 Fig). We also analyzed one cell line that shows no increase in miR-155 upon treatment, CP50-MEL (Fig 5). As expected, in this cell line only an effect on transcription was observed. Unfortunately, we were not able to delineate the cis-element that mediates IL-1ß induced-repression of MITF-M transcription in reporter assays (data not shown). This suggests that this effect is mediated by an element outside of the core promoter.


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)

Inverse correlation between the expression of MITF-M and that of miR-155 in melanoma cell lines incubated with IL-1ß.(A) The expression of MITF-M, Tyrosinase and miR-155 was analyzed by quantitative RT-PCR in 8 melanoma cell lines incubated with IL-1ß (10 ng/ml) for 4h or 24h. The results were normalized to ß-actin expression for MITF-M and Tyrosinase and to RNU44 for miR-155 (means ± SD for 3 independent experiments). (B) The expression of MITF-M and Tyrosinase proteins was analyzed by Western Blot in the same samples (1 of 3 independent experiments).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0122517.g005: Inverse correlation between the expression of MITF-M and that of miR-155 in melanoma cell lines incubated with IL-1ß.(A) The expression of MITF-M, Tyrosinase and miR-155 was analyzed by quantitative RT-PCR in 8 melanoma cell lines incubated with IL-1ß (10 ng/ml) for 4h or 24h. The results were normalized to ß-actin expression for MITF-M and Tyrosinase and to RNU44 for miR-155 (means ± SD for 3 independent experiments). (B) The expression of MITF-M and Tyrosinase proteins was analyzed by Western Blot in the same samples (1 of 3 independent experiments).
Mentions: In the cell lines that show upregulation of miR-155 by IL-1ß our results suggest that both reduced mRNA transcription and mRNA destabilization occur (S1 Fig). We also analyzed one cell line that shows no increase in miR-155 upon treatment, CP50-MEL (Fig 5). As expected, in this cell line only an effect on transcription was observed. Unfortunately, we were not able to delineate the cis-element that mediates IL-1ß induced-repression of MITF-M transcription in reporter assays (data not shown). This suggests that this effect is mediated by an element outside of the core promoter.

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