Biology subjects

Bignon, J.

Publications and source records attributed to Bignon, J..

3 recordsLinked to original sources

bioRxiv2024

The knockdown of the snoRNA-jouvence blocks the cell proliferation and leads to cell death of human primary cancerous glioblastoma cells

Cancer research aims to identify new therapeutic targets and provide patients with more effective therapies that generate fewer deleterious side effects. Previous studies have demonstrated the role of small nucleolar RNAs (snoRNAs) in many physiological and pathological cellular processes, including cancers. SnoRNAs are a group of non-coding RNAs involved in different post-transcriptional modifications of ribosomal RNAs. Recently, we have identified a new snoRNA, named jouvence (snoRNA-jou) in humans. Here, we characterize the effect of the knockdown of the snoRNA-jouvence by sh-lentivirus on human primary glioblastoma cells. The sh-lentivirus induces a significant decrease of cell proliferation, proportional to the amount of lentivirus used. For example, with a MOI-20, a decrease of more than 50% is observed after only 72 hours, and even up to 80% after 10 days. Moreover, a EdU proliferative test confirms this decrease in cell proliferation, while a TUNEL test reveals the presence of apoptotic cells. A RNA-Seq analysis, validated by RT-qPCR, reveals that the snoRNA-jou knockdown induces a significant deregulation of several key genes involved in the cell cycle regulation, such as cyclins B1, A2 and p21, indicating a cell cycle blockage. Altogether, these results allow hypothesising that the knockdown of the snoRNA-jouvence could potentially be use as a new anti-cancer treatment (sno-Therapy).

cancer biology↗

bioRxiv2020

jouvence, a new human H/ACA snoRNA involves in the control of cell proliferation and differentiation

Small nucleolar RNAs (snoRNAs) are non-coding RNAs conserved from archeobacteria to mammals. In humans, various snoRNAs have been associated with pathologies as well as with cancer. Recently in Drosophila, a new snoRNA named jouvence has been involved in lifespan. Since snoRNAs are well conserved through evolution, both structurally and functionally, jouvence orthologue has been identified in human, allowing hypothesizing that jouvence could display a similar function (increasing healthy lifespan) in human. Here, we report the characterization of the human snoRNA-jouvence, which was not yet annotated in the genome. We show, both in stably cancerous cell lines and in primary cells, that its overexpression stimulates the cell proliferation. In contrast, its knockdown, by siRNA leads to an opposite phenotype, a decrease in cell proliferation. Transcriptomic analysis reveals that overexpression of jouvence leads to a dedifferentiation signature of the cells, a cellular effect comparable to rejuvenation. Inversely, the knockdown of jouvence leads to a decrease of genes involved in ribosomes biogenesis and spliceosome in agreement with the canonical role of a H/ACA box snoRNA. In this context, jouvence could represent a now tool to fight against the deleterious effect of aging, as well as a new target in cancer therapy.

genetics↗

bioRxiv2019

Molecular and cellular dissection of the OSBP cycle through a fluorescent inhibitor

ORPphilins, natural molecules that strongly and selectively inhibit the growth of some cancer cell lines, are proposed to target intracellular lipid-transfer proteins of the Oxysterol-binding protein (OSBP) family. These conserved proteins exchange key lipids, such as cholesterol and phopsphatidylinositol-4-phosphate (PI(4)P), between organelle membranes. Among ORPphilins, molecules of the schweinfurthin family interfere with intracellular lipid distribution and metabolism, but their functioning at the molecular level is poorly understood. We report here that cell line sensitivity to schweinfurthin G (SWG) is inversely proportional to cellular level of OSBP. By taking advantage of the intrinsic fluorescence of SWG, we follow its fate in cell cultures and show that its incorporation at the TGN depends on OSBP cellular abundance. We report that SWG inhibits specifically the lipid exchange cycle of OSBP. As a consequence, post-Golgi trafficking, membrane cholesterol levels and PI(4)P turnover are affected. Finally, we demonstrate the direct binding of SWG into OSBP lipid-binding cavity by intermolecular FRET. Collectively these data describe for the first time a specific and intrinsically fluorescent pharmacological tool to dissect OSBP properties at the cellular and molecular levels.

cell biology↗