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MPV17 并不控制癌细胞增殖。

MPV17 does not control cancer cell proliferation.

机构信息

Laboratory of Biochemistry and Cell Biology (URBC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur (UNamur), Namur, Belgium.

Laboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium.

出版信息

PLoS One. 2020 Mar 10;15(3):e0229834. doi: 10.1371/journal.pone.0229834. eCollection 2020.

Abstract

MPV17 is described as a mitochondrial inner membrane channel. Although its function remains elusive, mutations in the MPV17 gene result in hepato-cerebral mitochondrial DNA depletion syndrome in humans. In 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 with two different shRNAs. However, 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 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-based gene silencing and clearly demonstrate the need to systematically perform a rescue experiment in order to ascertain the specific nature of the experimental results.

摘要

MPV17 被描述为一种线粒体内膜通道。尽管其功能仍不清楚,但 MPV17 基因的突变会导致人类肝脑线粒体 DNA 耗竭综合征。在这项研究中,我们表明 MPV17 沉默不会诱导癌细胞中线粒体 DNA 含量的耗竭。我们还表明,MPV17 并不控制癌细胞的增殖,尽管我们最初观察到在使用两种不同 shRNA 的五株 MPV17 沉默的癌细胞系中增殖率降低。然而,本文中进行的 shRNA 介导的 MPV17 敲低实验提供了关于增殖表型的误导性结果,只有挽救实验才能明确阐明 MPV17 在癌细胞增殖中的作用。因此,我们的结果强调了从基于慢病毒载体的基因沉默的工作中得出科学结论时需要谨慎,并清楚地表明需要系统地进行挽救实验,以确定实验结果的具体性质。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2186/7064194/b002718a7ca4/pone.0229834.g001.jpg

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