The tumour suppressor, miR-137, inhibits malignant melanoma migration by targetting the TBX3 transcription factor
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Published on: October 27, 2020
Jade Peres1, Eliza M Kwesi-Maliepaard1, Florian Rambow2
1Division of Cell Biology, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory, 7925, Cape Town, South Africa.
Abstract:
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.
Insights
MicroRNA-137 (miR-137) replacement therapy shows promise for treating malignant melanoma by targeting the oncogene TBX3. Restoring miR-137 levels may improve patient survival in this aggressive cancer.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- TBX3 is a transcription factor driving malignant melanoma, a treatment-resistant cancer.
- MicroRNA (miRNA) replacement therapy is a promising approach targeting oncogenes with potential for efficacy and minimal side effects.
Purpose of the Study:
- To investigate the relationship between miR-137 and TBX3 in melanoma.
- To evaluate miR-137 replacement as a potential therapeutic strategy for melanoma.
Main Methods:
- Correlation analysis of miR-137 and TBX3 mRNA levels in melanoma cell lines and patient cohorts.
- Luciferase reporter assays to confirm miR-137 binding to TBX3.
- In vitro studies using miR-137 mimics to assess effects on TBX3 expression, cell growth, and migration.
Main Results:
- Inverse correlation observed between miR-137 and TBX3 mRNA levels in melanoma.
- Low miR-137 and high TBX3 levels correlate with poor patient survival.
- miR-137 mimic reduced TBX3 levels and inhibited melanoma cell anchorage-independent growth and migration.
Conclusions:
- The miR-137/TBX3/E-cadherin axis is crucial in melanoma development.
- miR-137 replacement therapy is a potential therapeutic strategy for melanoma treatment.
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