Original ArticleThe tumour suppressor, miR-137, inhibits malignant melanoma migration by targetting the TBX3 transcription factor

- Anti-correlation of miR-137 and TBX3 levels in melanoma.
- Low miR-137 levels and high TBX3 levels are associated with a poor patient survival.
- miR-137 directly binds a highly conserved site in the TBX3 3′UTR.
- miR-137/TBX3/E-cadherin axis plays an important role in melanoma migration.
- miR-137 replacement is a therapeutic approach to treating TBX3-driven melanomas.

The transcription factor, TBX3, is a key driver of malignant melanoma and any drug that impacts its expression is likely to have an impact on the treatment of this highly aggressive and treatment resistant cancer. Replacement of miRNAs that target oncogenes has gained much attention as a therapy because it is anticipated to be effective with little side-effects since miRNAs are naturally occurring and often target large set of genes in the same oncogenic pathway. Here we show that miR-137 levels correlate inversely with TBX3 mRNA levels in a panel of melanoma cell lines and in a cohort of patients with primary melanoma. Low levels of miR-137 and high levels of TBX3 are shown to be associated with poor patient survival. We show that miR-137 binds a conserved site in the TBX3 3′ untranslated region and that a miR-137 mimic significantly reduces endogenous levels of TBX3 and inhibits anchorage independent growth and migration of malignant melanoma cells. Novel data are provided that the miR-137/TBX3/E-cadherin axis plays an important role in melanomagenesis and that miR-137 replacement is a potential therapeutic approach for treating melanomas.