Study of a regulation mechanism of miR-16 microRNA activity in uveal melanoma.
Gene Expression and Oncogenesis team
Under the direction of Pr Marie Dominique Galibert and Dr David Gilot.
Altered miRNA expression may be associated with the occurrence of diseases such as cancer. This is particularly the case when a miRNA with tumor suppressor activity is under-expressed. We have shown that miR-16, a potent tumor suppressor, is implicated in the aggressiveness of uveal melanoma, not by its level of expression but by a reduction in its activity (sequestered miRNA).
We have identified the RNAs interacting with miR-16 in uveal melanoma (miR-16 interactoma). The miR-16 interactome comprises the classical miR-16 targets, i.e. RNAs whose binding to miR-16 leads to their degradation, but also RNAs to which miR-16 binds and is sequestered.
This lack of degradation is explained by the fact that miR-16 binds to non canonical miR-16 response elements. We show that these non canonical bonds mobilize part of the miR-16 cell pool and consequently reduce its tumor suppressor activity. In addition, we confirm that the binding of miR-16 to a non canonical binding site can lead to overexpression of both RNA and protein.
Our evaluation of the tumor suppressor activity of miR- 16 (interactoma) predicts the survival of patients with uveal melanoma.
This work thus illustrates the importance of considering not only the expression of miRNAs but also their availability in order to evaluate their activity.
The jury will be composed of :
- Frédéric MOURIAUX PU-PH INSERM U1242, Président
- Stéphan VAGNER DR, Institut Curie, CNRS URM3348 Rapporteur
- Roger REZZONICO CR IPMC- CNRS 7275, Rapporteur
- Corine BERTOLOTTO DR, C3M INSERM U1065, Examinatrice
- Marina BOUSQUET CR UMR1037 INSERM ERL5294 CNRS, Examinatrice
- Marie-DominiqueGALIBERT PU-PH,IGDRUMR6290UR1- CNRS, Examinatrice
- David GILOT MCU INSERM U1242, Directeur de thèse