{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:20:06Z","timestamp":1791498006374,"version":"4.3.4"},"reference-count":37,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004097","name":"Fondation ARC pour la Recherche sur le Cancer","doi-asserted-by":"publisher","award":["ARCPJA32020060002114"],"award-info":[{"award-number":["ARCPJA32020060002114"]}],"id":[{"id":"10.13039\/501100004097","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ANR (Aging-jou)","award":["ARCPJA32020060002114"],"award-info":[{"award-number":["ARCPJA32020060002114"]}]},{"name":"CNRS","award":["ARCPJA32020060002114"],"award-info":[{"award-number":["ARCPJA32020060002114"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ncRNA"],"abstract":"<jats:p>Background\/Objectives: Cancer research aims to understand the cellular and molecular mechanisms involved, in order to identify new therapeutic targets and provide patients with more effective therapies that generate fewer side undesirable and toxic 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 identified a new snoRNA (jouvence), first in Drosophila, and thereafter, by homology, in humans. Methods: Here, we characterize the effect of the knockdown of jouvence by a sh-lentivirus on human primary patient-derived glioblastoma cells. Results: The sh-lentivirus anti-jouvence induces a significant decrease in cell proliferation and leads to cell death. EdU staining confirmed this decrease, while TUNEL also showed the presence of apoptotic cells. An RNA-Seq analysis revealed a decrease, in particular, in the level of BAALC, a gene known to potentiate the oncogenic ERK pathway and deregulating p21, leading to cell cycle blockage. Conclusions: Altogether, these results allow the hypothesis that the knockdown of jouvence could potentially be used as a new anti-cancer treatment (sno-Therapy), especially against glioblastoma and also, potentially, against acute myeloid leukemia (AML) due to the BAALC deregulation.<\/jats:p>","DOI":"10.3390\/ncrna11040054","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T12:09:53Z","timestamp":1752840593000},"page":"54","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Knockdown of the snoRNA-Jouvence Blocks the Proliferation and Leads to the Death of Human Primary Glioblastoma Cells"],"prefix":"10.3390","volume":"11","author":[{"given":"Lola","family":"Jaque-Cabrera","sequence":"first","affiliation":[{"name":"Institut des Neurosciences Paris-Saclay (Neuro-PSI), CNRS, UMR-9197, Universit\u00e9 Paris-Saclay, Campus CEA Saclay, 151 Route de la Rotonde, Batiment 151, 91400 Saclay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5862-6000","authenticated-orcid":false,"given":"Julia","family":"Buggiani","sequence":"additional","affiliation":[{"name":"Institut des Neurosciences Paris-Saclay (Neuro-PSI), CNRS, UMR-9197, Universit\u00e9 Paris-Saclay, Campus CEA Saclay, 151 Route de la Rotonde, Batiment 151, 91400 Saclay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6294-9671","authenticated-orcid":false,"given":"J\u00e9r\u00f4me","family":"Bignon","sequence":"additional","affiliation":[{"name":"Institut de Chimie des Substances Naturelles (ICSN), CNRS, UPR-2301, Universit\u00e9 Paris-Saclay, 91198 Gif-sur-Yvette, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Daira","sequence":"additional","affiliation":[{"name":"Laboratoire de M\u00e9canique des Contacts et des Structures (LaMCoS), INSA Lyon, CNRS, UMR5259, 69621 Villeurbanne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8009-5983","authenticated-orcid":false,"given":"Nathalie","family":"Bernoud-Hubac","sequence":"additional","affiliation":[{"name":"Laboratoire de M\u00e9canique des Contacts et des Structures (LaMCoS), INSA Lyon, CNRS, UMR5259, 69621 Villeurbanne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4041-5174","authenticated-orcid":false,"given":"Jean-Ren\u00e9","family":"Martin","sequence":"additional","affiliation":[{"name":"Institut des Neurosciences Paris-Saclay (Neuro-PSI), CNRS, UMR-9197, Universit\u00e9 Paris-Saclay, Campus CEA Saclay, 151 Route de la Rotonde, Batiment 151, 91400 Saclay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,18]]},"reference":[{"key":"ref_1","first-page":"3","article-title":"Glioblastoma Multiforme: A Review of its Epidemiology and Pathogenesis through Clinical Presentation and Treatment","volume":"18","author":"Hanif","year":"2017","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1968","DOI":"10.1016\/j.celrep.2017.10.070","article-title":"A Pan-cancer Analysis of the Expression and Clinical Relevance of Small Nucleolar RNAs in Human Cancer","volume":"21","author":"Gong","year":"2017","journal-title":"Cell Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s13277-014-2818-8","article-title":"Small nucleolar RNAs functioning and potential roles in cancer","volume":"36","author":"Thorenoor","year":"2014","journal-title":"Tumor Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.bbcan.2012.03.005","article-title":"Small nucleolar RNAs in cancer","volume":"1826","author":"Mannoor","year":"2012","journal-title":"Biochim. Biophys. Acta (BBA)-Rev. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1038\/nrc3195","article-title":"Are snoRNAs and snoRNA host genes new players in cancer?","volume":"12","author":"Williams","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Liang, J., Wen, J., Huang, Z., Chen, X.-P., Zhang, B.-X., and Chu, L. (2019). Small Nucleolar RNAs: Insight Into Their Function in Cancer. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.00587"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Van der Werf, J., Chin, C.V., and Fleming, N.I. (2021). SnoRNA in Cancer Progression, Metastasis and Immunotherapy Response. Biology, 10.","DOI":"10.3390\/biology10080809"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"101064","DOI":"10.1016\/j.jpha.2024.101064","article-title":"SnoRNAs: The promising targets for anti-tumor therapy","volume":"14","author":"Hu","year":"2024","journal-title":"J. Pharm. Anal."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0092-8674(02)00718-3","article-title":"Small Nucleolar RNAs: An Abundant Group of Noncoding RNAs with Diverse Cellular Functions","volume":"109","author":"Kiss","year":"2002","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.tibs.2013.01.002","article-title":"RNA pseudouridylation: New insights into an old modification","volume":"38","author":"Ge","year":"2013","journal-title":"Trends Biochem. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/nrc2819","article-title":"MYC as a regulator of ribosome biogenesis and protein synthesis","volume":"10","author":"Yetil","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2800","DOI":"10.1038\/s41388-018-0611-7","article-title":"Inhibitors of ribosome biogenesis repress the growth of MYCN-amplified neuroblastoma","volume":"38","author":"Hald","year":"2018","journal-title":"Oncogene"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1016\/j.celrep.2015.01.055","article-title":"Perturbation of Ribosome Biogenesis Drives Cells into Senescence through 5S RNP-Mediated p53 Activation","volume":"10","author":"Nishimura","year":"2015","journal-title":"Cell Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1038\/s41467-020-14784-1","article-title":"Jouvence a small nucleolar RNA required in the gut extends lifespan in Drosophila","volume":"11","author":"Arab","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Soul\u00e9, S., and Martin, J.R. (2020). ninaD regulates cholesterol homeostasis from the midgut which protects against neurodegeneration. BioRxiv, 11.","DOI":"10.1101\/2020.11.27.401059"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"El-Khoury, F., Bignon, J., and Martin, J.-R. (2020). jouvence, a new human snoRNA involved in the control of cell proliferation. BMC Genom., 21.","DOI":"10.1186\/s12864-020-07197-3"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Huh, H.D., Kim, D.H., Jeong, H.-S., and Park, H.W. (2019). Regulation of TEAD Transcription Factors in Cancer Biology. Cells, 8.","DOI":"10.3390\/cells8060600"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"13901","DOI":"10.1073\/pnas.241525498","article-title":"BAALC, the human member of a novel mammalian neuroectoderm gene lineage, is implicated in hematopoiesis and acute leukemia","volume":"98","author":"Tanner","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.1038\/leu.2015.137","article-title":"BAALC potentiates oncogenic ERK pathway through interactions with MEKK1 and KLF4","volume":"29","author":"Morita","year":"2015","journal-title":"Leukemia"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3289","DOI":"10.1038\/s41388-023-02836-x","article-title":"Dysregulation of cholesterol metabolism in cancer progression","volume":"42","author":"Liu","year":"2023","journal-title":"Oncogene"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1186\/s13287-020-01643-5","article-title":"High cholesterol induces apoptosis and autophagy through the ROS-activated AKT\/FOXO1 pathway in tendon-derived stem cells","volume":"11","author":"Li","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.cmet.2015.04.010","article-title":"snoRNA U17 Regulates Cellular Cholesterol Trafficking","volume":"21","author":"Jinn","year":"2015","journal-title":"Cell Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1002\/wrna.1266","article-title":"Small RNAs with big implications: New insights into H\/ACA snoRNA function and their role in human disease","volume":"6","author":"McMahon","year":"2015","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.molcel.2012.08.021","article-title":"Df31 Protein and snoRNAs Maintain Accessible Higher-Order Structures of Chromatin","volume":"48","author":"Schubert","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.semcdb.2020.03.009","article-title":"Mammalian cell cycle cyclins","volume":"107","author":"Malumbres","year":"2020","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/s41418-018-0246-9","article-title":"Mutant p53 as a guardian of the cancer cell","volume":"26","author":"Mantovani","year":"2019","journal-title":"Cell Death Differ."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s12672-016-0262-5","article-title":"The Contribution of Cholesterol and Its Metabolites to the Pathophysiology of Breast Cancer","volume":"7","author":"Baek","year":"2016","journal-title":"Horm. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"805","DOI":"10.3892\/ijo.2014.2246","article-title":"Cholesterol induces autophagic and apoptotic death in gastric carcinoma cells","volume":"44","author":"Lim","year":"2014","journal-title":"Int. J. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3799","DOI":"10.1038\/s41467-022-31135-4","article-title":"T cell cholesterol efflux suppresses apoptosis and senescence and increases atherosclerosis in middle aged mice","volume":"13","author":"Bazioti","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/sj.cdd.4402280","article-title":"Bax activation and stress-induced apoptosis delayed by the accumulation of cholesterol in mitochondrial membranes","volume":"15","author":"Montessuit","year":"2008","journal-title":"Cell Death Differ."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.cell.2011.12.017","article-title":"Mutant p53 Disrupts Mammary Tissue Architecture via the Mevalonate Pathway","volume":"148","author":"Mizuno","year":"2012","journal-title":"Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.cellbi.2005.10.022","article-title":"Induction of BAALC and down regulation of RAMP3 in astrocytes treated with differentiation inducers","volume":"30","author":"Moodbidri","year":"2006","journal-title":"Cell Biol. Int."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Sun, Y., Liu, Y., Ma, X., and Hu, H. (2021). The Influence of Cell Cycle Regulation on Chemotherapy. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136923"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"99","DOI":"10.5732\/cjc.012.10132","article-title":"Small nucleolar RNAs (snoRNAs) as potential non-invasive biomarkers for early cancer detection","volume":"32","author":"Chen","year":"2013","journal-title":"Chin. J. Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Deng, T., Gong, Y., Liao, X., Wang, X., Zhou, X., Zhu, G., and Mo, L. (2021). Integrative Analysis of a Novel Eleven-Small Nucleolar RNA Prognostic Signature in Patients With Lower Grade Glioma. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.650828"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"D353","DOI":"10.1093\/nar\/gkw1092","article-title":"KEGG: New perspectives on genomes, pathways, diseases and drugs","volume":"45","author":"Kanehisa","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"D590","DOI":"10.1093\/nar\/gky962","article-title":"New approach for understanding genome variations in KEGG","volume":"47","author":"Kanehisa","year":"2018","journal-title":"Nucleic Acids Res."}],"container-title":["Non-Coding RNA"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2311-553X\/11\/4\/54\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:12:08Z","timestamp":1760033528000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2311-553X\/11\/4\/54"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,18]]},"references-count":37,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["ncrna11040054"],"URL":"https:\/\/doi.org\/10.3390\/ncrna11040054","relation":{},"ISSN":["2311-553X"],"issn-type":[{"value":"2311-553X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,18]]}}}