Study of the putative role of MPV17 in cancer cell proliferation

Student thesis: Doc typesDocteur en Sciences


MPV17 is described as a mitochondrial inner membrane channel. Although its biological function remains elusive, mutations in the MPV17 gene result in hepatocerebral Mitochondrial DNA Depletion Syndrome (MDDS) 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 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 and HepG2 (hepatocellular carcinomas) and T98G (glioblastoma) cell lines, evocative of the hepatocerebral form of MPV17-related MDDS. We therefore hypothesize that ciRNAs might, at least partly, be accountable for the organ-specificity of the pathogenic phenotype seen in patients.
la date de réponse27 août 2020
langue originaleAnglais
L'institution diplômante
  • Universite de Namur
SuperviseurBenoit Muylkens (Président), Patricia Renard (Promoteur), Thierry Arnould (Copromoteur), Frédérique Coppée (Jury), Jean-Pierre Gillet (Jury) & Mustapha Najimi (Jury)

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