{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T04:17:42Z","timestamp":1774930662557,"version":"3.50.1"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T00:00:00Z","timestamp":1655683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011789","name":"Department of Science and Technology of Jilin Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011789","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Blocking ataxia telangiectasia mutated (ATM), a crucial player in DNA repair responses, has been proposed as a promising strategy in anti-cancer therapy. Most previous studies have focused on DNA damage response-related pathways after administration of ATM inhibitors. However, ATM inhibition could potentially influence a wide range of changes in gene expression, which remain poorly defined. Here, we report that administration of the ATM inhibitor KU60019 led to impaired migration and enhanced apoptosis in the ovarian cancer cell line SKOV3, accompanied by abnormally elevated O-GlcNAc transferase and O-GlcNAcase expression levels. In addition, KU60019 treatment significantly suppressed expression of <jats:italic>hsa-miR-542-5p<\/jats:italic> in SKOV3 cells. Up-regulation of <jats:italic>hsa-miR-542-5p<\/jats:italic> expression inhibited increases in OGT and OGA level, and reversed the effects of ATM inhibition on apoptosis and migration in SKOV3 cells. Finally, we found aberrant expression of <jats:italic>OGT<\/jats:italic> and <jats:italic>OGA<\/jats:italic> to be associated with ovarian cancer patient survival. Taken together, our results suggest that ATM inhibition may promote SKOV3 cell apoptosis <jats:italic>via<\/jats:italic> suppressing <jats:italic>hsa-miR-542-5p<\/jats:italic> and elevating <jats:italic>OGT<\/jats:italic> and <jats:italic>OGA<\/jats:italic> expression, providing new insights into the application of ATM inhibitors in cancer immunotherapy.<\/jats:p>","DOI":"10.3389\/fonc.2022.839508","type":"journal-article","created":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T06:39:47Z","timestamp":1655707187000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Blocking ATM Attenuates SKOV3 Cell Proliferation and Migration by Disturbing OGT\/OGA Expression via hsa-miR-542-5p"],"prefix":"10.3389","volume":"12","author":[{"given":"Ning","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miaomiao","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhanchuan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"87","DOI":"10.3322\/caac.21262","article-title":"Global Cancer Statistics, 2012","volume":"65","author":"Torre","year":"2015","journal-title":"CA: Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.soncn.2019.02.001","article-title":"Ovarian Cancer: An Integrated Review","volume":"35","author":"Stewart","year":"2019","journal-title":"Semin Oncol Nurs"},{"key":"B3","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.bpobgyn.2016.08.006","article-title":"Epidemiology of Epithelial Ovarian Cancer","volume":"41","author":"Webb","year":"2017","journal-title":"Best Pract Res Clin Obstet Gynaecol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"viii57","DOI":"10.1093\/annonc\/mdx442","article-title":"New Treatments in Ovarian Cancer","volume":"28","author":"Pujade-Lauraine","year":"2017","journal-title":"Ann Oncol Off J Eur Soc Med Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25112496","article-title":"Resolving DNA Damage: Epigenetic Regulation of DNA Repair","volume":"25","author":"Karakaidos","year":"2020","journal-title":"Molecules (Basel Switzerland)"},{"key":"B6","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1146\/annurev.biochem.73.011303.073723","article-title":"Molecular Mechanisms of Mammalian DNA Repair and the DNA Damage Checkpoints","volume":"73","author":"Sancar","year":"2004","journal-title":"Annu Rev Biochem"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.mct-15-0945","article-title":"ATM Mutations in Cancer: Therapeutic Implications","volume":"15","author":"Choi","year":"2016","journal-title":"Mol Cancer Ther"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29121","article-title":"Pharmacokinetics, Pharmacodynamics and Efficacy on Pediatric Tumors of the Glioma Radiosensitizer KU60019","volume":"136","author":"Vecchio","year":"2015","journal-title":"Int J Cancer"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-019-0941-2","article-title":"N-Myc Promotes Therapeutic Resistance Development of Neuroendocrine Prostate Cancer by Differentially Regulating miR-421\/ATM Pathway","volume":"18","author":"Yin","year":"2019","journal-title":"Mol Cancer"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.7150\/thno.27806","article-title":"Down-Regulation of OGT Promotes Cisplatin Resistance by Inducing Autophagy in Ovarian Cancer","volume":"8","author":"Zhou","year":"2018","journal-title":"Theranostics"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-018-0435-5","article-title":"O-GlcNAcylation Promotes Colorectal Cancer Metastasis via the miR-101-O-GlcNAc\/EZH2 Regulatory Feedback Circuit","volume":"38","author":"Jiang","year":"2019","journal-title":"Oncogene"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.7150\/thno.34024","article-title":"Fatty Acid-Induced CD36 Expression via O-GlcNAcylation Drives Gastric Cancer Metastasis","volume":"9","author":"Jiang","year":"2019","journal-title":"Theranostics"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2016.05.028","article-title":"O-GlcNAcylation in Cancer Biology: Linking Metabolism and Signaling","volume":"428","author":"Ferrer","year":"2016","journal-title":"J Mol Biol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.04.026","article-title":"O-GlcNAcylation Regulates Cancer Metabolism and Survival Stress Signaling via Regulation of the HIF-1 Pathway","volume":"54","author":"Ferrer","year":"2014","journal-title":"Mol Cell"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2015.00138","article-title":"Biosynthetic Machinery Involved in Aberrant Glycosylation: Promising Targets for Developing of Drugs Against Cancer","volume":"5","author":"Vasconcelos-Dos-Santos","year":"2015","journal-title":"Front Oncol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.302547","article-title":"Critical Role of O-Linked \u03b2-N-Acetylglucosamine Transferase in Prostate Cancer Invasion, Angiogenesis, and Metastasis","volume":"287","author":"Lynch","year":"2012","journal-title":"J Biol Chem"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bby054","article-title":"Trends in the Development of miRNA Bioinformatics Tools","volume":"20","author":"Chen","year":"2019","journal-title":"Brief Bioinf"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19123717","article-title":"miR-542-5p Attenuates Fibroblast Activation by Targeting Integrin \u03b16 in Silica-Induced Pulmonary Fibrosis","volume":"19","author":"Yuan","year":"2018","journal-title":"Int J Mol Sci"},{"key":"B19","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1186\/s12885-017-3646-1","article-title":"The Suppressive Role of miR-542-5p in NSCLC: The Evidence From Clinical Data and In Vivo Validation Using a Chick Chorioallantoic Membrane Model","volume":"17","author":"He","year":"2017","journal-title":"BMC Cancer"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.2147\/ott.s257329","article-title":"Pristimerin Suppressed Breast Cancer Progression via miR-542-5p\/DUB3 Axis","volume":"13","author":"Cheng","year":"2020","journal-title":"OncoTargets Ther"},{"key":"B21","doi-asserted-by":"publisher","first-page":"e12146","DOI":"10.1002\/jev2.12146","article-title":"Hypoxia-Stimulated ATM Activation Regulates Autophagy-Associated Exosome Release From Cancer-Associated Fibroblasts to Promote Cancer Cell Invasion","volume":"10","author":"Xi","year":"2021","journal-title":"J extracellular vesicles"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.120.266122","article-title":"MK-8719, a Novel and Selective O-GlcNAcase Inhibitor That Reduces the Formation of Pathological Tau and Ameliorates Neurodegeneration in a Mouse Model of Tauopathy","volume":"374","author":"Wang","year":"2020","journal-title":"J Pharmacol Exp Ther"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222011073","article-title":"OSMI-1 Enhances TRAIL-Induced Apoptosis Through ER Stress and NF-\u03bab Signaling in Colon Cancer Cells","volume":"22","author":"Lee","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B24","doi-asserted-by":"publisher","first-page":"9227","DOI":"10.1038\/s41598-018-27521-y","article-title":"Validation of miRNA Prognostic Power in Hepatocellular Carcinoma Using Expression Data of Independent Datasets","volume":"8","author":"Nagy","year":"2018","journal-title":"Sci Rep"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.07.031","article-title":"A Pattern-Based Method for the Identification of MicroRNA Binding Sites and Their Corresponding Heteroduplexes","volume":"126","author":"Miranda","year":"2006","journal-title":"Cell"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr483","article-title":"KOBAS 2.0: A Web Server for Annotation and Identification of Enriched Pathways and Diseases","volume":"39","author":"Xie","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"B27","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/s41420-021-00489-x","article-title":"Reduced O-GlcNAcylation of SNAP-23 Promotes Cisplatin Resistance by Inducing Exosome Secretion in Ovarian Cancer","volume":"7","author":"Qian","year":"2021","journal-title":"Cell Death Discov"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.6244","article-title":"O-GlcNAcylation Promotes Migration and Invasion in Human Ovarian Cancer Cells via the RhoA\/ROCK\/MLC Pathway","volume":"15","author":"Niu","year":"2017","journal-title":"Mol Med Rep"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.734533","article-title":"Changes in O-Linked N-Acetylglucosamine (O-GlcNAc) Homeostasis Activate the P53 Pathway in Ovarian Cancer Cells","volume":"291","author":"de Queiroz","year":"2016","journal-title":"J Biol Chem"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19092750","article-title":"Hyperglycemia-Associated Dysregulation of O-GlcNAcylation and HIF1A Reduces Anticancer Action of Metformin in Ovarian Cancer Cells (SKOV-3)","volume":"19","author":"Rogalska","year":"2018","journal-title":"Int J Mol Sci"},{"key":"B31","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1038\/s41419-020-02999-5","article-title":"Mutual Regulation Between OGT and XIAP to Control Colon Cancer Cell Growth and Invasion","volume":"11","author":"Seo","year":"2020","journal-title":"Cell Death Dis"},{"key":"B32","doi-asserted-by":"publisher","first-page":"e109","DOI":"10.1038\/oncsis.2014.24","article-title":"OGA Heterozygosity Suppresses Intestinal Tumorigenesis in Apc(min\/+) Mice","volume":"3","author":"Yang","year":"2014","journal-title":"Oncogenesis"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(20)31176-4","article-title":"Progression-Free Survival in the ICON8 Trial","volume":"396","author":"Balieiro Anastacio da Costa","year":"2020","journal-title":"Lancet (London England)"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2021.03.017","article-title":"Predictors of Response, Progression-Free Survival, and Overall Survival in Patients With Lung Cancer Treated With Immune Checkpoint Inhibitors","volume":"16","author":"Memmott","year":"2021","journal-title":"J Thorac Oncol Off Publ Int Assoc Study Lung Cancer"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djp369","article-title":"Detecting an Overall Survival Benefit That is Derived From Progression-Free Survival","volume":"101","author":"Broglio","year":"2009","journal-title":"J Natl Cancer Institute"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.839508\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T06:39:50Z","timestamp":1655707190000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.839508\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,20]]},"references-count":35,"alternative-id":["10.3389\/fonc.2022.839508"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2022.839508","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,20]]},"article-number":"839508"}}