Défense de thèse de doctorat - sciences biologiques

Study of the putative role of MPV17 in cancer cell proliferation

Jury

• Benoït MUYLKENS (UNamur), President
• Patsy RENARD (UNamur), Secretary
• Mustapha NAJIMI (UCLouvain)
• Frédérique COPPEE (UMons)
• Jean-Pierre GILLET (UNamur)
• Thierry ARNOULD (UNamur)
  

Abstract

MPV17 is described as a mitochondrial inner membrane channel. Although its function remains elusive, mutations in the MPV17 gene result in hepatocerebral mitochondrial DNA depletion syndrome in humans. In the first part of this study, we show that MPV17 silencing does not induce depletion in mitochondrial DNA content in cancer cells. We also show that MPV17 does not control cancer cell proliferation despite the fact that we initially observed a reduced proliferation rate in five MPV17-silenced cancer cell lines. ShRNA-mediated MPV17 knockdown performed in this work provided misguiding results regarding the resulting proliferation phenotype and only a rescue experiment was able to shed definitive light on the non-implication of MPV17 in cancer cell proliferation. Our results therefore emphasize the caution that is required when scientific conclusions are drawn from a work based on lentiviral vector-mediated gene silencing and clearly demonstrate the need to systematically perform a rescue experiment in order to ascertain the specific nature of the experimental results. In the second part of this study, we investigated the putative existence of circular RNAs (ciRNAs) derived from the MPV17 gene. CiRNAs are covalently closed RNA loop structures that have become rising stars in the disease research. In this work, we identified many putative MPV17 ciRNAs, in need of further validation. Among them, one turned out to be common to Huh7 (hepatocellular carcinoma) and T98G (glioblastoma cells) cells, evocative of the hepatocerebral form of MPV17-related MDDS. We therefore hypothesize that ciRNAs might be in part accountable for the organ-specificity of the pathogenic phenotype seen in patients.

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