MicroRNA-155, Induced by Interleukin-1β, represses the expression of microphthalmia-associated transcription factor (MITF-M) in melanoma cells

Loss of expression of surface antigens represents a significant problem for cancer immunotherapy. Microphthalmia-associated transcription factor (MITF-M) regulatesmelanocyte fate by driving expression ofmany differentiation genes, whose protein products can be recognized by cytolytic T lymphocytes.We previously reported that interleukin-1β (IL-1β) can downregulate MITF-M levels. Here we show that downregulation ofMITF-M expression by IL-1β was paralleled by an upregulation ofmiR-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-1β-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 ofmelanoma. Taken together, our results indicate that MITF-M downregulation by inflammatory stimuli might be partly due tomiR-155 upregulation. This could represent a novel mechanism ofmelanoma immune escape in an inflammatory microenvironment.