Figure 9. A model summarizing the regulation and role of miR-211 in melanoma.

MITF, a transcription factor with tumor-suppressor activity, is active in melanocytes, where it is required for the expression of TRPM1, the structural gene for melatonin-1. miR-211 gene is located within the sixth intron of TRPM1, which is co-transcribed with the TRPM1 transcript, is processed to active miR-211 and subsequently the latter acts on the 3′-UTR of KCNMA1 transcript. We propose that inhibition of KCNMA1 translation is needed for preventing the development of invasive melanoma. MITF activity is low in melanoma cells, which is expected to reduce TRPM1 as well as miR-211 transcription, therefore would induce the expression of KCNMA1. While it is widely held on the basis of expression pattern alone that TRPM1 is a putative tumor suppressor, we show that miR-211, contained within the pre-mRNA of TRPM1 transcript, also has a tumor suppressor activity through its negative regulation on KCNMA1.