{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T23:04:54Z","timestamp":1781305494912,"version":"3.54.1"},"reference-count":90,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81973585"],"award-info":[{"award-number":["81973585"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Metabolic-related diseases are chronic diseases caused by multiple factors, such as genetics and the environment. These diseases are difficult to cure and seriously affect human health. Squalene epoxidase (SQLE), the second rate-limiting enzyme in cholesterol synthesis, plays an important role in cholesterol synthesis and alters the gut microbiota and tumor immunity. Research has shown that SQLE is expressed in many tissues and organs and is involved in the occurrence and development of various metabolic-related diseases, such as cancer, nonalcoholic fatty liver disease, diabetes mellitus, and obesity. SQLE inhibitors, such as terbinafine, NB598, natural compounds, and their derivatives, can effectively ameliorate fungal infections, nonalcoholic fatty liver disease, and cancer. In this review, we provide an overview of recent research progress on the role of SQLE in metabolic-related diseases. Further research on the regulation of SQLE expression is highly important for developing drugs for the treatment of metabolic-related diseases with good pharmacological activity.<\/jats:p>","DOI":"10.7717\/peerj.18522","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T12:01:42Z","timestamp":1732276902000},"page":"e18522","source":"Crossref","is-referenced-by-count":12,"title":["Targeting squalene epoxidase in the treatment of metabolic-related diseases: current research and future directions"],"prefix":"10.7717","volume":"12","author":[{"given":"Mingzhu","family":"Chen","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences, Chengdu University of Chinese Medicine, Chengdu, Sichuan Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqi","family":"Yang","sequence":"additional","affiliation":[{"name":"Harbin Medical University, Department of Pharmacology, College of Pharmacy, Harbin, Heilongjiang Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiting","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Chengdu University of Chinese Medicine, Chengdu, Sichuan Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"He","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Chengdu University of Chinese Medicine, Chengdu, Sichuan Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian","family":"Du","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Chengdu University of Chinese Medicine, Chengdu, Sichuan Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4443","published-online":{"date-parts":[[2024,11,22]]},"reference":[{"issue":"3","key":"10.7717\/peerj.18522\/ref-1","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1006\/bbrc.2000.2217","article-title":"Green tea polyphenols: novel and potent inhibitors of squalene epoxidase","volume":"268","author":"Abe","year":"2000","journal-title":"Biochemical and Biophysical Research Communications"},{"issue":"1","key":"10.7717\/peerj.18522\/ref-2","doi-asserted-by":"publisher","first-page":"102342","DOI":"10.1016\/j.bpobgyn.2023.102342","article-title":"The epidemiology of obesity in reproduction","volume":"89","author":"Ahmed","year":"2023","journal-title":"Best Practice & Research Clinical Obstetrics & Gynaecology"},{"issue":"1","key":"10.7717\/peerj.18522\/ref-3","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/0005-2760(77)90056-X","article-title":"Squalene epoxidase and oxidosqualene lanosterol-cyclase activities in cholesterogenic and non-cholesterogenic tissues","volume":"487","author":"Astruc","year":"1977","journal-title":"Biochimica et Biophysica Acta (BBA)-Lipids and Lipid Metabolism"},{"issue":"4","key":"10.7717\/peerj.18522\/ref-4","doi-asserted-by":"publisher","first-page":"465","DOI":"10.18388\/abp.1995_4900","article-title":"Ergosterol biosynthesis inhibition: a target for antifungal agents","volume":"42","author":"Barrett-Bee","year":"1995","journal-title":"Acta Biochimica Polonica"},{"key":"10.7717\/peerj.18522\/ref-5","doi-asserted-by":"publisher","first-page":"990672","DOI":"10.3389\/fonc.2022.990672","article-title":"Loss of the Fbw7 tumor suppressor rewires cholesterol metabolism in cancer cells leading to activation of the PI3K-AKT signalling axis","volume":"12","author":"Bengoechea-Alonso","year":"2022","journal-title":"Frontiers in Oncology"},{"issue":"1","key":"10.7717\/peerj.18522\/ref-6","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1038\/s41467-019-08866-y","article-title":"The shape of human squalene epoxidase expands the arsenal against cancer","volume":"10","author":"Brown","year":"2019","journal-title":"Nature Communications"},{"issue":"1","key":"10.7717\/peerj.18522\/ref-7","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1146\/annurev-biochem-062917-011852","article-title":"Retrospective on cholesterol homeostasis: the central role of scap","volume":"87","author":"Brown","year":"2018","journal-title":"Annual Review of Biochemistry"},{"issue":"8","key":"10.7717\/peerj.18522\/ref-8","doi-asserted-by":"publisher","first-page":"2805","DOI":"10.3390\/nu13082805","article-title":"Metabolic derangement in pediatric patient with obesity: the role of ketogenic diet as therapeutic tool","volume":"13","author":"Calcaterra","year":"2021","journal-title":"Nutrients"},{"issue":"437","key":"10.7717\/peerj.18522\/ref-9","doi-asserted-by":"publisher","first-page":"eaat3741","DOI":"10.1126\/scitranslmed.aat3741","article-title":"Cholesterol, cancer, and rebooting a treatment for athlete\u2019s foot","volume":"10","author":"Chua","year":"2018","journal-title":"Science Translational Medicine"},{"issue":"49","key":"10.7717\/peerj.18522\/ref-10","doi-asserted-by":"publisher","first-page":"19959","DOI":"10.1074\/jbc.M117.794230","article-title":"A conserved degron containing an amphipathic helix regulates the cholesterol-mediated turnover of human squalene monooxygenase, a rate-limiting enzyme in cholesterol synthesis","volume":"292","author":"Chua","year":"2017","journal-title":"Journal of Biological Chemistry"},{"key":"10.7717\/peerj.18522\/ref-11","doi-asserted-by":"publisher","first-page":"100731","DOI":"10.1016\/j.jbc.2021.100731","article-title":"The mammalian cholesterol synthesis enzyme squalene monooxygenase is proteasomally truncated to a constitutively active form","volume":"296","author":"Coates","year":"2021","journal-title":"Journal of Biological Chemistry"},{"key":"10.7717\/peerj.18522\/ref-12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.coi.2018.08.001","article-title":"Loss of sterol metabolic homeostasis triggers inflammasomes\u2014how and why","volume":"56","author":"Dang","year":"2019","journal-title":"Current Opinion in Immunology"},{"issue":"2","key":"10.7717\/peerj.18522\/ref-13","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1007\/s10549-015-3474-4","article-title":"Race-associated biological differences among Luminal A breast tumors","volume":"152","author":"D\u2019Arcy","year":"2015","journal-title":"Breast Cancer Research and Treatment"},{"issue":"10","key":"10.7717\/peerj.18522\/ref-14","doi-asserted-by":"publisher","first-page":"3464","DOI":"10.2337\/db14-1314","article-title":"Alterations of a cellular cholesterol metabolism network are a molecular feature of obesity-related type 2 diabetes and cardiovascular disease","volume":"64","author":"Ding","year":"2015","journal-title":"Diabetes"},{"issue":"13","key":"10.7717\/peerj.18522\/ref-15","doi-asserted-by":"publisher","first-page":"4103","DOI":"10.7150\/ijbs.85724","article-title":"Squalene epoxidase\/SQLE is a candidate target for treatment of colorectal cancers with p53 mutation and elevated c-MYC expression","volume":"19","author":"Du","year":"2023","journal-title":"International Journal of Biological Sciences"},{"issue":"1","key":"10.7717\/peerj.18522\/ref-16","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s12933-018-0728-6","article-title":"Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007\u20132017","volume":"17","author":"Einarson","year":"2018","journal-title":"Cardiovascular Diabetology"},{"issue":"2","key":"10.7717\/peerj.18522\/ref-17","doi-asserted-by":"publisher","first-page":"107444","DOI":"10.1016\/j.jdiacomp.2019.107444","article-title":"RNA-Seq analysis of the pathogenesis of STZ-induced male diabetic mouse liver","volume":"34","author":"Ge","year":"2020","journal-title":"Journal of Diabetes and its Complications"},{"key":"10.7717\/peerj.18522\/ref-18","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.3389\/fphys.2018.01051","article-title":"Mulberry leaf regulates differentially expressed genes in diabetic mice liver based on RNA-Seq analysis","volume":"9","author":"Ge","year":"2018","journal-title":"Frontiers in Physiology"},{"issue":"3","key":"10.7717\/peerj.18522\/ref-19","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1016\/j.cmet.2011.01.015","article-title":"Cholesterol-dependent degradation of squalene monooxygenase, a control point in cholesterol synthesis beyond HMG-CoA reductase","volume":"13","author":"Gill","year":"2011","journal-title":"Cell Metabolism"},{"key":"10.7717\/peerj.18522\/ref-20","doi-asserted-by":"publisher","first-page":"723224","DOI":"10.3389\/fphys.2021.723224","article-title":"Sterols, oxysterols, and accessible cholesterol: signalling for homeostasis, in immunity and during development","volume":"12","author":"Griffiths","year":"2021","journal-title":"Frontiers in Physiology"},{"issue":"6","key":"10.7717\/peerj.18522\/ref-21","doi-asserted-by":"publisher","first-page":"1662","DOI":"10.1093\/jn\/131.6.1662","article-title":"Garlic and garlic-derived compounds inhibit human squalene monooxygenase","volume":"131","author":"Gupta","year":"2001","journal-title":"The Journal of Nutrition"},{"issue":"8","key":"10.7717\/peerj.18522\/ref-22","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1002\/cac2.12187","article-title":"Squalene epoxidase promotes colorectal cancer cell proliferation through accumulating calcitriol and activating CYP24A1-mediated MAPK signaling","volume":"41","author":"He","year":"2021","journal-title":"Cancer Communications"},{"key":"10.7717\/peerj.18522\/ref-23","doi-asserted-by":"publisher","first-page":"e9812","DOI":"10.7717\/peerj.9812","article-title":"Using bioinformatics and metabolomics to identify altered granulosa cells in patients with diminished ovarian reserve","volume":"8","author":"He","year":"2020","journal-title":"PeerJ"},{"issue":"5","key":"10.7717\/peerj.18522\/ref-24","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1038\/sj.bjc.6604556","article-title":"Squalene epoxidase, located on chromosome 8q24. 1, is upregulated in 8q+ breast cancer and indicates poor clinical outcome in stage I and II disease","volume":"99","author":"Helms","year":"2008","journal-title":"British Journal of Cancer"},{"issue":"46","key":"10.7717\/peerj.18522\/ref-25","doi-asserted-by":"publisher","first-page":"27533","DOI":"10.1074\/jbc.M115.675181","article-title":"The regulatory domain of squalene monooxygenase contains a re-entrant loop and senses cholesterol via a conformational change","volume":"290","author":"Howe","year":"2015","journal-title":"Journal of Biological Chemistry"},{"issue":"7","key":"10.7717\/peerj.18522\/ref-26","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1016\/j.bbalip.2017.03.009","article-title":"New insights into cellular cholesterol acquisition: promoter analysis of human HMGCR and SQLE, two key control enzymes in cholesterol synthesis","volume":"1862","author":"Howe","year":"2017","journal-title":"Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids"},{"issue":"2","key":"10.7717\/peerj.18522\/ref-27","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1038\/s42255-020-0174-0","article-title":"Cholesterol metabolism in cancer: mechanisms and therapeutic opportunities","volume":"2","author":"Huang","year":"2020","journal-title":"Nature Metabolism"},{"issue":"3","key":"10.7717\/peerj.18522\/ref-28","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1111\/cas.15248","article-title":"Squalene synthase predicts poor prognosis in stage I\u2013III colon adenocarcinoma and synergizes squalene epoxidase to promote tumor progression","volume":"113","author":"Jiang","year":"2022","journal-title":"Cancer Science"},{"issue":"4","key":"10.7717\/peerj.18522\/ref-29","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1053\/j.gastro.2020.09.009","article-title":"Reduction of squalene epoxidase by cholesterol accumulation accelerates colorectal cancer progression and metastasis","volume":"160","author":"Jun","year":"2021","journal-title":"Gastroenterology"},{"issue":"1","key":"10.7717\/peerj.18522\/ref-30","doi-asserted-by":"publisher","first-page":"5066","DOI":"10.1038\/s41467-021-25325-9","article-title":"MiR-205-driven downregulation of cholesterol biosynthesis through SQLE-inhibition identifies therapeutic vulnerability in aggressive prostate cancer","volume":"12","author":"Kalogirou","year":"2021","journal-title":"Nature Communications"},{"issue":"5","key":"10.7717\/peerj.18522\/ref-31","doi-asserted-by":"publisher","first-page":"632","DOI":"10.3390\/jcm8050632","article-title":"Squalene epoxidase correlates E-cadherin expression and overall survival in colorectal cancer patients: the impact on prognosis and correlation to clinicopathologic features","volume":"8","author":"Kim","year":"2019","journal-title":"Journal of Clinical Medicine"},{"issue":"21","key":"10.7717\/peerj.18522\/ref-32","doi-asserted-by":"publisher","first-page":"8178","DOI":"10.3390\/ijms21218178","article-title":"Prevention of diabetes and cardiovascular disease in obesity","volume":"21","author":"La Sala","year":"2020","journal-title":"International Journal of Molecular Sciences"},{"issue":"2","key":"10.7717\/peerj.18522\/ref-33","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/S0022-2275(20)31684-9","article-title":"Inhibition of human squalene monooxygenase by tellurium compounds: evidence of interaction with vicinal sulfhydryls","volume":"42","author":"Laden","year":"2001","journal-title":"Journal of Lipid Research"},{"issue":"1","key":"10.7717\/peerj.18522\/ref-34","doi-asserted-by":"publisher","first-page":"20230632","DOI":"10.1515\/med-2023-0632","article-title":"Hsa_circ_0028007 regulates the progression of nasopharyngeal carcinoma through the miR-1179\/SQLE axis","volume":"18","author":"Li","year":"2023","journal-title":"Open Medicine"},{"issue":"11","key":"10.7717\/peerj.18522\/ref-35","doi-asserted-by":"publisher","first-page":"2253","DOI":"10.1136\/gutjnl-2021-325851","article-title":"Squalene epoxidase drives cancer cell proliferation and promotes gut dysbiosis to accelerate colorectal carcinogenesis","volume":"71","author":"Li","year":"2022a","journal-title":"Gut"},{"issue":"9","key":"10.7717\/peerj.18522\/ref-36","doi-asserted-by":"publisher","first-page":"3576","DOI":"10.7150\/ijbs.68216","article-title":"Upregulation of SQLE contributes to poor survival in head and neck squamous cell carcinoma","volume":"18","author":"Li","year":"2022b","journal-title":"International Journal of Biological Sciences"},{"key":"10.7717\/peerj.18522\/ref-37","doi-asserted-by":"publisher","first-page":"4709","DOI":"10.2147\/CMAR.S305719","article-title":"High SQLE expression and gene amplification correlates with poor prognosis in head and neck squamous cell carcinoma","volume":"13","author":"Liu","year":"2021","journal-title":"Cancer Management and Research"},{"issue":"1","key":"10.7717\/peerj.18522\/ref-38","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s13045-019-0841-3","article-title":"MiR-612 regulates invadopodia of hepatocellular carcinoma by HADHA-mediated lipid reprogramming","volume":"13","author":"Liu","year":"2020","journal-title":"Journal of Hematology & Oncology"},{"issue":"437","key":"10.7717\/peerj.18522\/ref-39","doi-asserted-by":"publisher","first-page":"eaap9840","DOI":"10.1126\/scitranslmed.aap9840","article-title":"Squalene epoxidase drives NAFLD-induced hepatocellular carcinoma and is a pharmaceutical target","volume":"10","author":"Liu","year":"2018","journal-title":"Science Translational Medicine"},{"issue":"7","key":"10.7717\/peerj.18522\/ref-40","doi-asserted-by":"publisher","first-page":"2467","DOI":"10.1053\/j.gastro.2021.02.051","article-title":"Squalene epoxidase induces nonalcoholic steatohepatitis via binding to carbonic anhydrase III and is a therapeutic target","volume":"160","author":"Liu","year":"2021","journal-title":"Gastroenterology"},{"issue":"1","key":"10.7717\/peerj.18522\/ref-41","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1038\/s41467-018-07959-4","article-title":"A chemical biology screen identifies a vulnerability of neuroendocrine cancer cells to SQLE inhibition","volume":"10","author":"Mahoney","year":"2019","journal-title":"Nature Communications"},{"issue":"1","key":"10.7717\/peerj.18522\/ref-42","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1006\/geno.1997.4825","article-title":"Localization of the squalene epoxidase gene (SQLE) to human chromosome region 8q24.1","volume":"44","author":"Nagai","year":"1997","journal-title":"Genomics"},{"issue":"8","key":"10.7717\/peerj.18522\/ref-43","doi-asserted-by":"publisher","first-page":"115103","DOI":"10.1016\/j.taap.2020.115103","article-title":"Preclinical toxicology profile of squalene epoxidase inhibitors","volume":"401","author":"Nagaraja","year":"2020","journal-title":"Toxicology and Applied Pharmacology"},{"issue":"2","key":"10.7717\/peerj.18522\/ref-44","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1016\/j.jhep.2021.05.003","article-title":"The Chinese Society of Hepatology position statement on the redefinition of fatty liver disease","volume":"75","author":"Nan","year":"2021","journal-title":"Journal of Hepatology"},{"issue":"15","key":"10.7717\/peerj.18522\/ref-45","doi-asserted-by":"publisher","first-page":"8228","DOI":"10.1073\/pnas.2003388117","article-title":"Squalene and cholesterol in the balance at the ER membrane","volume":"117","author":"Nathan","year":"2020","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"1","key":"10.7717\/peerj.18522\/ref-46","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/s41467-018-07928-x","article-title":"Structure and inhibition mechanism of the catalytic domain of human squalene epoxidase","volume":"10","author":"Padyana","year":"2019","journal-title":"Nature Communications"},{"issue":"3","key":"10.7717\/peerj.18522\/ref-47","doi-asserted-by":"publisher","first-page":"e95","DOI":"10.1038\/oncsis.2014.8","article-title":"Frequent MYC coamplification and DNA hypomethylation of multiple genes on 8q in 8p11-p12-amplified breast carcinomas","volume":"3","author":"Parris","year":"2014","journal-title":"Oncogenesis"},{"issue":"3","key":"10.7717\/peerj.18522\/ref-48","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1128\/AAC.19.3.390","article-title":"In vivo antimycotic activity of naftifine","volume":"19","author":"Petranyi","year":"1981","journal-title":"Antimicrobial Agents and Chemotherapy"},{"issue":"34","key":"10.7717\/peerj.18522\/ref-49","doi-asserted-by":"publisher","first-page":"4750","DOI":"10.1038\/s41388-018-0281-5","article-title":"The cancer-associated microprotein CASIMO1 controls cell proliferation and interacts with squalene epoxidase modulating lipid droplet formation","volume":"37","author":"Polycarpou-Schwarz","year":"2018","journal-title":"Oncogene"},{"issue":"1","key":"10.7717\/peerj.18522\/ref-50","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1007\/s12672-023-00630-5","article-title":"Circ_0000182 promotes cholesterol synthesis and proliferation of stomach adenocarcinoma cells by targeting miR-579-3p\/SQLE axis","volume":"14","author":"Qian","year":"2023","journal-title":"Discover Oncology"},{"issue":"2","key":"10.7717\/peerj.18522\/ref-51","doi-asserted-by":"publisher","first-page":"2002232","DOI":"10.1002\/advs.202002232","article-title":"A novel long non-coding RNA lnc030 maintains breast cancer stem cell stemness by stabilizing SQLE mRNA and increasing cholesterol synthesis","volume":"8","author":"Qin","year":"2021","journal-title":"Advanced Science"},{"issue":"2","key":"10.7717\/peerj.18522\/ref-52","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1093\/abbs\/gmw127","article-title":"SQLE induces epithelial-to-mesenchymal transition by regulating of miR-133b in esophageal squamous cell carcinoma","volume":"49","author":"Qin","year":"2017","journal-title":"Acta Biochimica et Biophysica Sinica"},{"issue":"1","key":"10.7717\/peerj.18522\/ref-53","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1111\/j.1749-6632.1988.tb40405.x","article-title":"Mechanism of action and biochemical selectivity of allylamine antimycotic agents","volume":"544","author":"Ryder","year":"1988","journal-title":"Annals of the New York Academy of Sciences"},{"issue":"3","key":"10.7717\/peerj.18522\/ref-54","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1042\/bst0190774","article-title":"Squalene epoxidase as a target for the allylamines","volume":"19","author":"Ryder","year":"1991","journal-title":"Biochemical Society Transactions"},{"issue":"s39","key":"10.7717\/peerj.18522\/ref-55","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1111\/j.1365-2133.1992.tb00001.x","article-title":"Terbinafine: Mode of action and properties of the squalene epoxidase inhibition","volume":"126","author":"Ryder","year":"1992","journal-title":"British Journal of Dermatology"},{"issue":"2","key":"10.7717\/peerj.18522\/ref-56","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1007\/s11906-018-0812-z","article-title":"The global epidemic of the metabolic syndrome","volume":"20","author":"Saklayen","year":"2018","journal-title":"Current Hypertension Reports"},{"issue":"1","key":"10.7717\/peerj.18522\/ref-57","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/S0014-2999(01)01411-X","article-title":"Effect of FR194738, a potent inhibitor of squalene epoxidase, on cholesterol metabolism in HepG2 cells","volume":"431","author":"Sawada","year":"2001","journal-title":"European Journal of Pharmacology"},{"issue":"3","key":"10.7717\/peerj.18522\/ref-58","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1016\/j.bmcl.2003.11.072","article-title":"Synthesis and biological activity of a novel squalene epoxidase inhibitor, FR194738","volume":"14","author":"Sawada","year":"2004","journal-title":"Bioorganic & Medicinal Chemistry Letters"},{"issue":"2","key":"10.7717\/peerj.18522\/ref-59","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1097\/CRD.0b013e3181885905","article-title":"Pharmacologic inhibition of squalene synthase and other downstream enzymes of the cholesterol synthesis pathway: a new therapeutic approach to treatment of hypercholesterolemia","volume":"17","author":"Seiki","year":"2009","journal-title":"Cardiology in Review"},{"issue":"17","key":"10.7717\/peerj.18522\/ref-60","doi-asserted-by":"publisher","first-page":"3032","DOI":"10.1158\/0008-5472.CAN-21-3822","article-title":"Squalene epoxidase metabolic dependency is a targetable vulnerability in castration-resistant prostate cancer","volume":"82","author":"Shangguan","year":"2022","journal-title":"Cancer Research"},{"issue":"51","key":"10.7717\/peerj.18522\/ref-61","doi-asserted-by":"publisher","first-page":"17549","DOI":"10.1074\/jbc.REV120.010723","article-title":"Post-translational control of the long and winding road to cholesterol","volume":"295","author":"Sharpe","year":"2020","journal-title":"Journal of Biological Chemistry"},{"issue":"7","key":"10.7717\/peerj.18522\/ref-62","doi-asserted-by":"publisher","first-page":"2436","DOI":"10.1074\/jbc.RA118.005069","article-title":"Cholesterol increases protein levels of the E3 ligase MARCH6 and thereby stimulates protein degradation","volume":"294","author":"Sharpe","year":"2019","journal-title":"Journal of Biological Chemistry"},{"issue":"1","key":"10.7717\/peerj.18522\/ref-63","doi-asserted-by":"publisher","first-page":"1073274820914663","DOI":"10.1177\/1073274820914663","article-title":"High squalene epoxidase in tumors predicts worse survival in patients with hepatocellular carcinoma: integrated bioinformatic analysis on NAFLD and HCC","volume":"27","author":"Shen","year":"2020","journal-title":"Cancer Control: Journal of The Moffitt Cancer Center"},{"issue":"53","key":"10.7717\/peerj.18522\/ref-64","doi-asserted-by":"publisher","first-page":"38163","DOI":"10.1074\/jbc.274.53.38163","article-title":"The N-terminal K homology domain of the poly(rC)-binding protein is a major determinant for binding to the poliovirus 5\u2032-untranslated region and acts as an inhibitor of viral translation","volume":"274","author":"Silvera","year":"1999","journal-title":"Journal of Biological Chemistry"},{"issue":"1","key":"10.7717\/peerj.18522\/ref-65","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s13058-016-0713-5","article-title":"Cholesterol biosynthesis pathway as a novel mechanism of resistance to estrogen deprivation in estrogen receptor-positive breast cancer","volume":"18","author":"Simigdala","year":"2016","journal-title":"Breast Cancer Research"},{"issue":"6","key":"10.7717\/peerj.18522\/ref-66","doi-asserted-by":"publisher","first-page":"586","DOI":"10.3390\/ph14060586","article-title":"Dipeptidyl peptidase (DPP)-IV inhibitors with antioxidant potential isolated from natural sources: a novel approach for the management of diabetes","volume":"14","author":"Singh","year":"2021","journal-title":"Pharmaceuticals"},{"key":"10.7717\/peerj.18522\/ref-67","doi-asserted-by":"publisher","first-page":"708699","DOI":"10.3389\/fgene.2021.708699","article-title":"Construction and validation of a novel ferroptosis-related prognostic model for acute myeloid leukemia","volume":"12","author":"Song","year":"2022","journal-title":"Frontiers in Genetics"},{"issue":"6","key":"10.7717\/peerj.18522\/ref-68","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1038\/bjc.2014.385","article-title":"Unbiased analysis of pancreatic cancer radiation resistance reveals cholesterol biosynthesis as a novel target for radiosensitisation","volume":"111","author":"Souchek","year":"2014","journal-title":"British Journal of Cancer"},{"issue":"8","key":"10.7717\/peerj.18522\/ref-69","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1093\/carcin\/bgx058","article-title":"Cholesterol uptake and regulation in high-grade and lethal prostate cancers","volume":"38","author":"Stopsack","year":"2017","journal-title":"Carcinogenesis"},{"issue":"16","key":"10.7717\/peerj.18522\/ref-70","doi-asserted-by":"publisher","first-page":"4785","DOI":"10.1158\/0008-5472.CAN-16-0903","article-title":"Cholesterol metabolism and prostate cancer lethality","volume":"76","author":"Stopsack","year":"2016","journal-title":"Cancer Research"},{"issue":"3","key":"10.7717\/peerj.18522\/ref-71","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1152\/physiolgenomics.00183.2004","article-title":"Microarray gene expression analysis of the Fob3b obesity QTL identifies positional candidate gene Sqle and perturbed cholesterol and glycolysis pathways","volume":"20","author":"Stylianou","year":"2005","journal-title":"Physiological Genomics"},{"issue":"1","key":"10.7717\/peerj.18522\/ref-72","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1007\/s12032-015-0717-5","article-title":"Increased lanosterol turnover: a metabolic burden for daunorubicin-resistant leukemia cells","volume":"33","author":"St\u00e4ubert","year":"2016","journal-title":"Medical Oncology"},{"issue":"8","key":"10.7717\/peerj.18522\/ref-73","doi-asserted-by":"publisher","first-page":"6173","DOI":"10.1007\/s13277-015-3301-x","article-title":"Squalene epoxidase (SQLE) promotes the growth and migration of the hepatocellular carcinoma cells","volume":"36","author":"Sui","year":"2015","journal-title":"Tumor Biology"},{"issue":"10","key":"10.7717\/peerj.18522\/ref-74","doi-asserted-by":"publisher","first-page":"e52537","DOI":"10.15252\/embr.202152537","article-title":"p53 transcriptionally regulates SQLE to repress cholesterol synthesis and tumor growth","volume":"22","author":"Sun","year":"2021","journal-title":"EMBO Reports"},{"issue":"7483","key":"10.7717\/peerj.18522\/ref-75","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1038\/nature12986","article-title":"The multilayered complexity of ceRNA crosstalk and competition","volume":"505","author":"Tay","year":"2014","journal-title":"Nature"},{"issue":"3","key":"10.7717\/peerj.18522\/ref-76","doi-asserted-by":"publisher","first-page":"e0249187","DOI":"10.1371\/journal.pone.0249187","article-title":"Compositional change of gut microbiome and osteocalcin expressing endothelial progenitor cells in patients with coronary artery disease","volume":"16","author":"Toya","year":"2021","journal-title":"PLOS ONE"},{"issue":"5","key":"10.7717\/peerj.18522\/ref-77","doi-asserted-by":"publisher","first-page":"2169","DOI":"10.1046\/j.1471-4159.1995.64052169.x","article-title":"Tellurite specifically affects squalene epoxidase: investigations examining the mechanism of tellurium-induced neuropathy","volume":"64","author":"Wagner","year":"1995","journal-title":"Journal of Neurochemistry"},{"issue":"13","key":"10.7717\/peerj.18522\/ref-78","doi-asserted-by":"publisher","first-page":"3636","DOI":"10.1111\/jcmm.17347","article-title":"SQLE facilitates the pancreatic cancer progression via the lncRNA-TTN-AS1\/miR-133b\/SQLE axis","volume":"26","author":"Wang","year":"2022","journal-title":"Journal of Cellular and Molecular Medicine"},{"issue":"1","key":"10.7717\/peerj.18522\/ref-79","doi-asserted-by":"publisher","first-page":"1379861","DOI":"10.1080\/16546628.2017.1379861","article-title":"Polygala tenuifolia extract inhibits lipid accumulation in 3T3-L1 adipocytes and high-fat diet-induced obese mouse model and affects hepatic transcriptome and gut microbiota profiles","volume":"61","author":"Wang","year":"2017","journal-title":"Food & Nutrition Research"},{"key":"10.7717\/peerj.18522\/ref-80","doi-asserted-by":"publisher","first-page":"19202","DOI":"10.1002\/jcb.29250","article-title":"Identification of differentially expressed genes and functional annotations associated with metastases of the uveal melanoma","volume":"120","author":"Xu","year":"2019","journal-title":"Journal of Cellular Biochemistry"},{"issue":"8","key":"10.7717\/peerj.18522\/ref-81","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1038\/s41419-023-05987-7","article-title":"SQLE promotes pancreatic cancer growth by attenuating ER stress and activating lipid rafts-regulated Src\/PI3K\/Akt signaling pathway","volume":"14","author":"Xu","year":"2023","journal-title":"Cell Death & Disease"},{"issue":"7","key":"10.7717\/peerj.18522\/ref-82","doi-asserted-by":"publisher","first-page":"1670","DOI":"10.1016\/S0021-9258(19)77144-0","article-title":"Studies on squalene epoxidase of rat liver","volume":"245","author":"Yamamoto","year":"1970","journal-title":"Journal of Biological Chemistry"},{"key":"10.7717\/peerj.18522\/ref-83","doi-asserted-by":"publisher","first-page":"655889","DOI":"10.3389\/fcell.2021.655889","article-title":"MYC enhances cholesterol biosynthesis and supports cell proliferation through SQLE","volume":"9","author":"Yang","year":"2021","journal-title":"Frontiers in Cell and Developmental Biology"},{"issue":"4","key":"10.7717\/peerj.18522\/ref-84","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1158\/2159-8290.CD-22-0455","article-title":"Targeting microglial metabolic rewiring synergizes with immune-checkpoint blockade therapy for glioblastoma","volume":"13","author":"Ye","year":"2023","journal-title":"Cancer Discovery"},{"key":"10.7717\/peerj.18522\/ref-85","doi-asserted-by":"publisher","first-page":"864244","DOI":"10.3389\/fimmu.2022.864244","article-title":"SQLE, a key enzyme in cholesterol metabolism, correlates with tumor immune infiltration and immunotherapy outcome of pancreatic adenocarcinoma","volume":"13","author":"You","year":"2022","journal-title":"Frontiers in Immunology"},{"issue":"3","key":"10.7717\/peerj.18522\/ref-86","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/j.cmet.2014.01.019","article-title":"Cholesteryl ester accumulation induced by PTEN loss and PI3K\/AKT activation underlies human prostate cancer aggressiveness","volume":"19","author":"Yue","year":"2014","journal-title":"Cell Metabolism"},{"issue":"7","key":"10.7717\/peerj.18522\/ref-87","doi-asserted-by":"publisher","first-page":"3874","DOI":"10.3390\/ijms25073874","article-title":"Squalene epoxidase: its regulations and links with cancers","volume":"25","author":"Zhang","year":"2024","journal-title":"International Journal of Molecular Sciences"},{"issue":"4","key":"10.7717\/peerj.18522\/ref-88","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1111\/1759-7714.12087","article-title":"Expression and significance of squalene epoxidase in squamous lung cancerous tissues and pericarcinoma tissues","volume":"5","author":"Zhang","year":"2014","journal-title":"Thoracic Cancer"},{"issue":"2","key":"10.7717\/peerj.18522\/ref-89","doi-asserted-by":"publisher","first-page":"111512","DOI":"10.1016\/j.yexcr.2019.111512","article-title":"OSBPL2 deficiency upregulate SQLE expression increasing intracellular cholesterol and cholesteryl ester by AMPK\/SP1 and SREBF2 signalling pathway","volume":"383","author":"Zhang","year":"2019","journal-title":"Experimental Cell Research"},{"key":"10.7717\/peerj.18522\/ref-90","doi-asserted-by":"publisher","first-page":"938502","DOI":"10.3389\/fonc.2022.938502","article-title":"Targeting the key cholesterol biosynthesis enzyme squalene monooxygenasefor cancer therapy","volume":"12","author":"Zou","year":"2022","journal-title":"Frontiers in Oncology"}],"container-title":["PeerJ"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/peerj.com\/articles\/18522.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/18522.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/18522.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/18522.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T12:01:48Z","timestamp":1732276908000},"score":1,"resource":{"primary":{"URL":"https:\/\/peerj.com\/articles\/18522"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,22]]},"references-count":90,"alternative-id":["10.7717\/peerj.18522"],"URL":"https:\/\/doi.org\/10.7717\/peerj.18522","archive":["CLOCKSS","LOCKSS","Portico"],"relation":{},"ISSN":["2167-8359"],"issn-type":[{"value":"2167-8359","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,22]]},"article-number":"e18522"}}