{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T16:49:22Z","timestamp":1774975762787,"version":"3.50.1"},"reference-count":32,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the development fund of Lequn Branch, The First Hospital of Jilin University"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Ataxia telangiectasia mutated (ATM) blockage can induce apoptosis in ovarian cancer. However, the molecular mechanisms underlying this process remain poorly understood. In this study, ovarian cancer cells (SKOV3) were treated with an ATM inhibitor (KU60019) for 24 hours, and the fold changes of DGAT1 and hsa-miR-1273g-3p were quantified by real-time quantitative polymerase chain reaction (RT-qPCR). Gene Ontology (GO) and pathway enrichment analyses of DGAT1-associated functions were performed. Hsa-miR-1273g-3p mimics were used to investigate the relationship between DGAT1 and hsa-miR-1273g-3p in ovarian cancer cells under ATM inhibitor treatment, and cell apoptosis rate, viability, and migration were detected. The\u00a0DGAT1 inhibitor reversed KU60019-induced migration impairment in SKOV3 cells. Finally, Kaplan-Meier analysis showed the correlation between DGAT1 level and survival in ovarian cancer patients. We found that ATM blockage significantly suppressed hsa-miR-1273g-3p level and elevated DGAT1 level in SKOV3 cells. DGAT1 was enriched in cytokine receptor interaction, T cell receptor signaling pathway, and cell apoptosis. Hsa-miR-1273g-3p mimics reversed suppression of DGAT1 and impaired cell viability induced by KU60019. Higher levels of DGAT1 associated with worse survival in ovarian cancer patients. KU60019 induced ovarian cancer cell impairment by enhancing DGAT1 level and suppressing hsa-miR-1273g-3p level. Our results demonstrate the antitumor effect of KU60019 in ovarian cancer depended on miR1273g-3p\/DGAT1 axis.<\/jats:p>","DOI":"10.1371\/journal.pone.0325213","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T17:30:00Z","timestamp":1750786200000},"page":"e0325213","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["KU60019 inhibits ovarian cancer progression by targeting DGAT1\/has-miR-1273g-3p axis"],"prefix":"10.1371","volume":"20","author":[{"given":"Zhanchuan","family":"Ma","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rongjing","family":"Dang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4206-1782","authenticated-orcid":true,"given":"Guodong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"issue":"9","key":"pone.0325213.ref001","first-page":"972","article-title":"NCCN guidelines\u00ae insights: ovarian cancer, Version 3.2022","volume":"20","author":"DK Armstrong","year":"2022","journal-title":"JNCCN"},{"issue":"2","key":"pone.0325213.ref002","doi-asserted-by":"crossref","first-page":"416","DOI":"10.5530\/ijper.54.2.47","article-title":"Apoptosis of HeLa cells via Caspase-3 expression induced by chitosan-based nanoparticles of annona squamosa leaf extract: in vitro study","volume":"54","author":"A Fadholly","year":"2020","journal-title":"Indian J Pharmaceutical Educ Res"},{"issue":"6","key":"pone.0325213.ref003","doi-asserted-by":"crossref","first-page":"817","DOI":"10.5530\/pj.2022.14.173","article-title":"An in silico study to explore the role of EGFR in ovarian cancer","volume":"14","author":"V Jakhmola","year":"2023","journal-title":"Pharmacogn J"},{"issue":"8","key":"pone.0325213.ref004","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1080\/15548627.2020.1805860","article-title":"ATM loss disrupts the autophagy-lysosomal pathway","volume":"17","author":"A Cheng","year":"2021","journal-title":"Autophagy"},{"key":"pone.0325213.ref005","doi-asserted-by":"crossref","first-page":"107391","DOI":"10.1016\/j.pharmthera.2019.07.002","article-title":"ATM in DNA repair in cancer","volume":"203","author":"MH Jin","year":"2019","journal-title":"Pharmacol Ther"},{"issue":"7","key":"pone.0325213.ref006","doi-asserted-by":"crossref","first-page":"2470","DOI":"10.1021\/acs.molpharmaceut.1c00166","article-title":"Sensors and inhibitors for the detection of Ataxia Telangiectasia Mutated (ATM) protein kinase","volume":"18","author":"C Huang","year":"2021","journal-title":"Mol Pharm"},{"key":"pone.0325213.ref007","doi-asserted-by":"crossref","first-page":"749472","DOI":"10.3389\/fphar.2022.749472","article-title":"Novel diagnostic and therapeutic options for KMT2A-rearranged acute leukemias","volume":"13","author":"BA Lopes","year":"2022","journal-title":"Front Pharmacol"},{"issue":"1","key":"pone.0325213.ref008","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1038\/s41598-023-28185-z","article-title":"ATM inhibitor KU60019 synergistically sensitizes lung cancer cells to topoisomerase II poisons by multiple mechanisms","volume":"13","author":"J Shu","year":"2023","journal-title":"Sci Rep"},{"key":"pone.0325213.ref009","doi-asserted-by":"crossref","first-page":"839508","DOI":"10.3389\/fonc.2022.839508","article-title":"Blocking ATM attenuates SKOV3 cell proliferation and migration by disturbing OGT\/OGA expression via hsa-miR-542-5p","volume":"12","author":"N Wang","year":"2022","journal-title":"Front Oncol"},{"issue":"2","key":"pone.0325213.ref010","doi-asserted-by":"crossref","DOI":"10.1016\/j.cmet.2020.06.002","article-title":"Targeting DGAT1 ameliorates glioblastoma by increasing fat catabolism and oxidative stress","volume":"32","author":"X Cheng","year":"2020","journal-title":"Cell Metab"},{"issue":"2","key":"pone.0325213.ref011","doi-asserted-by":"crossref","first-page":"166","DOI":"10.5483\/BMBRep.2022-0201","article-title":"Triglyceride induces DNA damage leading to monocyte death by activating caspase-2 and caspase-8","volume":"56","author":"BC Jung","year":"2023","journal-title":"BMB Rep"},{"issue":"1","key":"pone.0325213.ref012","doi-asserted-by":"crossref","first-page":"3035","DOI":"10.1038\/s41598-019-39537-z","article-title":"DGAT1 inhibitor suppresses prostate tumor growth and migration by regulating intracellular lipids and non-centrosomal MTOC protein GM130","volume":"9","author":"F Nardi","year":"2019","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0325213.ref013","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1186\/s12885-021-07976-5","article-title":"Up-regulation of DGAT1 in cancer tissues and tumor-infiltrating macrophages influenced survival of patients with gastric cancer","volume":"21","author":"P He","year":"2021","journal-title":"BMC Cancer"},{"key":"pone.0325213.ref014","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1186\/s12864-016-2858-0","article-title":"Abstracts from the 3rd International Genomic Medicine Conference (3rd IGMC 2015): Jeddah, Kingdom of Saudi Arabia. 30 November - 3 December 2015","volume":"17","author":"JW Shay","year":"2016","journal-title":"BMC genomics"},{"key":"pone.0325213.ref015","first-page":"6636791","article-title":"DGAT1 expression promotes ovarian cancer progression and is associated with poor prognosis","volume":"2021","author":"L Xia","year":"2021","journal-title":"J Immunol Res"},{"issue":"4","key":"pone.0325213.ref016","doi-asserted-by":"crossref","first-page":"484","DOI":"10.56499\/jppres21.1047_9.4.484","article-title":"Molecular docking study of sea urchin (Arbacia lixula) peptides as multi-target inhibitor for non-small cell lung cancer (NSCLC) associated proteins","volume":"9","author":"MH Widyananda","year":"2021","journal-title":"J Pharm Pharmacogn Res"},{"issue":"5","key":"pone.0325213.ref017","doi-asserted-by":"crossref","first-page":"601","DOI":"10.3390\/biom14050601","article-title":"Palmitic acid exerts anti-tumorigenic activities by modulating cellular stress and lipid droplet formation in endometrial cancer","volume":"14","author":"Z Zhao","year":"2024","journal-title":"Biomolecules"},{"key":"pone.0325213.ref018","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkx247","article-title":"GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses","volume":"45","author":"Z Tang","year":"2017","journal-title":"Nucleic Acids Res"},{"issue":"3","key":"pone.0325213.ref019","first-page":"100625","article-title":"Integrated analysis of public datasets for the discovery and validation of survival-associated genes in solid tumors","volume":"5","author":"B Gy\u0151rffy","year":"2024","journal-title":"Innovation (Camb)"},{"issue":"21","key":"pone.0325213.ref020","article-title":"TIMER: a web server for comprehensive analysis of tumor-infiltrating immune cells","volume":"77","author":"T Li","year":"2017","journal-title":"Cancer Res"},{"key":"pone.0325213.ref021","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.05005","article-title":"Predicting effective microRNA target sites in mammalian mRNAs","volume":"4","author":"V Agarwal","year":"2015","journal-title":"Elife"},{"issue":"1","key":"pone.0325213.ref022","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1158\/1535-7163.MCT-19-0474","article-title":"Synergism between ATM and PARP1 inhibition involves DNA damage and abrogating the G2 DNA damage checkpoint","volume":"19","author":"JPY Mak","year":"2020","journal-title":"Mol Cancer Ther"},{"issue":"3","key":"pone.0325213.ref023","first-page":"2718","article-title":"Effects of KIF2A on the prognosis of nasopharyngeal carcinoma and nasopharyngeal carcinoma cells","volume":"18","author":"Q Zhang","year":"2019","journal-title":"Oncology Letters"},{"issue":"3","key":"pone.0325213.ref024","doi-asserted-by":"crossref","first-page":"164","DOI":"10.3390\/nu8030164","article-title":"Altered skeletal muscle fatty acid handling in subjects with impaired glucose tolerance as compared to impaired fasting glucose","volume":"8","author":"GH Goossens","year":"2016","journal-title":"Nutrients"},{"issue":"2","key":"pone.0325213.ref025","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1007\/s13577-020-00473-0","article-title":"Comprehensive upstream and downstream regulatory analyses identify miR-675-3p as a potential prognostic biomarker in melanoma","volume":"34","author":"C-C Zhao","year":"2021","journal-title":"Hum Cell"},{"issue":"1","key":"pone.0325213.ref026","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12943-021-01480-x","article-title":"Hsa_circ_0003258 promotes prostate cancer metastasis by complexing with IGF2BP3 and sponging miR-653-5p","volume":"21","author":"Y-Z Yu","year":"2022","journal-title":"Mol Cancer"},{"key":"pone.0325213.ref027","doi-asserted-by":"crossref","first-page":"106230","DOI":"10.1016\/j.biocel.2022.106230","article-title":"Ataxia-telangiectasia mutated and ataxia telangiectasia and Rad3-related kinases as therapeutic targets and stratification indicators for prostate cancer","volume":"147","author":"C Gulliver","year":"2022","journal-title":"Int J Biochem Cell Biol"},{"key":"pone.0325213.ref028","doi-asserted-by":"crossref","first-page":"44","DOI":"10.3389\/fonc.2020.00044","article-title":"Clinical significance of circulating miR-1273g-3p and miR-122-5p in pancreatic cancer","volume":"10","author":"T Mazza","year":"2020","journal-title":"Front Oncol"},{"issue":"10","key":"pone.0325213.ref029","doi-asserted-by":"crossref","first-page":"4305","DOI":"10.18632\/aging.203883","article-title":"MRTF-A-mediated protection against amyloid-\u03b2-induced neuronal injury correlates with restoring autophagy via miR-1273g-3p\/mTOR axis in Alzheimer models","volume":"14","author":"W Zhang","year":"2022","journal-title":"Aging (Albany NY)"},{"issue":"16","key":"pone.0325213.ref030","doi-asserted-by":"crossref","DOI":"10.1016\/j.molcel.2022.06.003","article-title":"An oncogenic JMJD6-DGAT1 axis tunes the epigenetic regulation of lipid droplet formation in clear cell renal cell carcinoma","volume":"82","author":"J Zhou","year":"2022","journal-title":"Mol Cell"},{"issue":"1","key":"pone.0325213.ref031","doi-asserted-by":"crossref","first-page":"100880","DOI":"10.1016\/j.xcrm.2022.100880","article-title":"DGKB mediates radioresistance by regulating DGAT1-dependent lipotoxicity in glioblastoma","volume":"4","author":"H Kang","year":"2023","journal-title":"Cell Rep Med"},{"issue":"12","key":"pone.0325213.ref032","doi-asserted-by":"crossref","first-page":"110995","DOI":"10.1016\/j.celrep.2022.110995","article-title":"Oxidative stress from DGAT1 oncoprotein inhibition in melanoma suppresses tumor growth when ROS defenses are also breached","volume":"39","author":"DJ Wilcock","year":"2022","journal-title":"Cell Rep"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0325213","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T17:30:08Z","timestamp":1750786208000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0325213"}},"subtitle":[],"editor":[{"given":"Jaswinder","family":"Singh","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,6,24]]},"references-count":32,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6,24]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0325213","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,24]]}}}