Société Française de Biochimie et Biologie Moléculaire

MARCH 2023 - Sophie MOCKLY

Institut de Recherches Cliniques de Montréal (IRCM)
"A rationalized definition of general tumor suppressor microRNAs excluded miR-34a" 
Nucleic Acid Res. 50, 4703-4712 DOI:10.1093/nar/gkac277

Mockly S., Houbron E. & Seitz H.



Sophie Mockly, 29 years old, obtained her PhD Degree from the University of Montpellier in Biology-Health in December 2021. After graduating with an Agronomic Science Engineering Degree in genetics and genomics at Agrocampus Ouest and a Master Degree in molecular and cellular biology at the University of Rennes, she joined the team of Dr Hervé Seitz at the Institute of Human Genetics of Montpellier (CNRS-University of Montpellier). During her PhD, she studied the systemic impact of miRNAs in cellular models by combining her skills in molecular biology and bioinformatics. In particular, her work led her to focus on the reciprocal regulation between miRNAs and their targets, as well as on the discrepancies between molecular analyses and phenotypic characterizations of miRNAs. At the end of 2022, Sophie has joined Dr. Martin Sauvageau's team at the Montreal Clinical Research Institute (Canada) as a Postdoctoral Fellow to study the molecular levers of lncRNA action and their physiological impact during the development and in diseases.



Adresse: Institut de Recherches Cliniques de Montréal (IRCM)
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Résumé de l'article

While several microRNAs (miRNAs) have been proposed to act as tumor suppressors, a consensual definition of tumor suppressing miRNAs is still missing. Similarly to coding genes, we propose that tumor suppressor miRNAs must show evidence of genetic or epigenetic inactivation in cancers, and exhibit an anti-tumorigenic (e.g., anti-proliferative) activity under endogenous expression levels. Here we observe that this definition excludes the most extensively studied tumor suppressor candidate miRNA, miR-34a. In analyzable cancer types, miR-34a does not appear to be down-regulated in primary tumors relatively to normal adjacent tissues. Deletion of miR-34a is occasionally found in human cancers, but it does not seem to be driven by an anti-tumorigenic activity of the miRNA, since it is not observed upon smaller, miR-34a-specific alterations. Its anti-proliferative action was observed upon large, supra-physiological transfection of synthetic miR-34a in cultured cells, and our data indicates that endogenous miR-34a levels do not have such an effect. Our results therefore argue against a general tumor suppressive function for miR-34a, providing an explanation to the lack of efficiency of synthetic miR-34a administration against solid tumors.