{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T15:05:10Z","timestamp":1784387110598,"version":"3.55.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T00:00:00Z","timestamp":1653264000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T00:00:00Z","timestamp":1653264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LQ18H070006"],"award-info":[{"award-number":["LQ18H070006"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Zhejiang Provincial Medical and Health Technology Project","award":["2019RC069"],"award-info":[{"award-number":["2019RC069"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Biol Rep"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Nonalcoholic fatty liver disease (NAFLD) is a major risk factor for hepatocellular carcinoma, and alterations in miRNA expression are related to the development of NAFLD. However, the role of miRNAs in regulating the development of NAFLD is still poorly understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used qRT-PCR to detect the level of miR-103-3p in both cell and mouse models of NAFLD. Biochemical assays, DCF-DA assays, Oil red O staining and HE staining were used to detect the role of miR-103-3p in NAFLD development. Target genes of miR-103-3p were predicted using the TargetScan database and verified by qRT-PCR, western blot and dual-luciferase assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The expression of miR-103-3p increased in both NAFLD model cells and liver tissues from the NAFLD mouse model. Inhibition of miR-103-3p significantly alleviated the accumulation of lipid droplets in free fatty acid-treated L02 cells and liver tissues from mice with NAFLD. Inhibition of miR-103-3p reduced the contents of H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>, TG, ALT, and AST and ROS production while increasing the ATP content. Moreover, the miR-103-3p antagomir alleviated liver tissue lesions in mice with NAFLD. Further studies identified ACOX1, a key enzyme for the oxidation and decomposition of fatty acids, as a direct target of miR-103-3p.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings identified a negative regulatory mechanism between ACOX1 and miR-103-3p that promotes the pathogenesis of NAFLD and suggested that inhibition of miR-103-3p may be a potential treatment strategy for NAFLD.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s11033-022-07515-w","type":"journal-article","created":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T18:03:41Z","timestamp":1653329021000},"page":"7297-7305","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["MiR-103-3p promotes hepatic steatosis to aggravate nonalcoholic fatty liver disease by targeting of ACOX1"],"prefix":"10.1007","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7823-0522","authenticated-orcid":false,"given":"Jiexia","family":"Ding","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caixia","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"Cen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siying","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifei","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,23]]},"reference":[{"key":"7515_CR1","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/s41575-020-00366-5","volume":"18","author":"S Francque","year":"2020","unstructured":"Francque S, Szabo G, Abdelmalek MF et al (2020) Nonalcoholic steatohepatitis: the role of peroxisome proliferator-activated receptors. Nat Rev Gastroenterol Hepatol 18:24\u201339","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"7515_CR2","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1038\/s41591-018-0104-9","volume":"24","author":"SL Friedman","year":"2018","unstructured":"Friedman SL, Neuschwander-Tetri BA, Rinella M et al (2018) Mechanisms of NAFLD development and therapeutic strategies. Nat Med 24:908\u2013922","journal-title":"Nat Med"},{"key":"7515_CR3","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1038\/nrgastro.2017.32","volume":"14","author":"NL Gluchowski","year":"2017","unstructured":"Gluchowski NL, Becuwe M, Walther TC et al (2017) Lipid droplets and liver disease: from basic biology to clinical implications. Nat Rev Gastroenterol Hepatol 14:343\u2013355","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"7515_CR4","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1038\/s41574-019-0256-9","volume":"15","author":"L Hodson","year":"2019","unstructured":"Hodson L, Gunn PJ (2019) The regulation of hepatic fatty acid synthesis and partitioning: the effect of nutritional state. Nat Rev Endocrinol 15:689\u2013700","journal-title":"Nat Rev Endocrinol"},{"key":"7515_CR5","doi-asserted-by":"publisher","first-page":"2065","DOI":"10.1136\/gutjnl-2018-318146","volume":"68","author":"M Gjorgjieva","year":"2019","unstructured":"Gjorgjieva M, Sobolewski C, Dolicka D et al (2019) miRNAs and NAFLD: from pathophysiology to therapy. Gut 68:2065\u20132079","journal-title":"Gut"},{"key":"7515_CR6","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1136\/gutjnl-2016-311526","volume":"66","author":"T Hardy","year":"2016","unstructured":"Hardy T, Zeybel M, Day CP et al (2016) Plasma DNA methylation: a potential biomarker for stratification of liver fibrosis in non-alcoholic fatty liver disease. Gut 66:1321\u20131328","journal-title":"Gut"},{"key":"7515_CR7","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1152\/physrev.00041.2015","volume":"96","author":"J Beermann","year":"2016","unstructured":"Beermann J, Piccoli MT, Viereck J et al (2016) Non-coding RNAs in development and disease: background, mechanisms, and therapeutic approaches. Physiol Rev 96:1297\u20131325","journal-title":"Physiol Rev"},{"key":"7515_CR8","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/nrd.2016.246","volume":"16","author":"R Rupaimoole","year":"2017","unstructured":"Rupaimoole R, Slack FJ (2017) MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov 16:203\u2013222","journal-title":"Nat Rev Drug Discov"},{"key":"7515_CR9","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.addr.2018.01.009","volume":"129","author":"Q Su","year":"2018","unstructured":"Su Q, Kumar V, Sud N et al (2018) Role of MicroRNAs in the pathogenesis and treatment of progressive liver injury in NAFLD and liver fibrosis. Adv Drug Deliv Rev 129:54\u201363","journal-title":"Adv Drug Deliv Rev"},{"key":"7515_CR10","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1016\/j.jhep.2018.08.008","volume":"69","author":"CH Liu","year":"2018","unstructured":"Liu CH, Ampuero J, Gil-G\u00f3mez A et al (2018) miRNAs in patients with non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol 69:1335\u20131348","journal-title":"J Hepatol"},{"key":"7515_CR11","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1136\/gutjnl-2016-312869","volume":"67","author":"G Hanin","year":"2017","unstructured":"Hanin G, Yayon N, Tzur Y et al (2017) miRNA-132 induces hepatic steatosis and hyperlipidaemia by synergistic multitarget suppression. Gut 67:1124\u20131134","journal-title":"Gut"},{"key":"7515_CR12","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1002\/hep.31428","volume":"73","author":"H Xu","year":"2020","unstructured":"Xu H, Tian Y, Tang D et al (2020) An endoplasmic reticulum stress-microRNA-26a feedback circuit in nonalcoholic fatty liver disease. Hepatology 73:1327\u20131345","journal-title":"Hepatology"},{"key":"7515_CR13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/15548627.2020.1797280","volume":"17","author":"DH Lee","year":"2021","unstructured":"Lee DH, Park SH, Ahn J et al (2021) Mir214-3p and Hnf4a\/Hnf4\u03b1 reciprocally regulate Ulk1 expression and autophagy in nonalcoholic hepatic steatosis. Autophagy 17:1\u201317","journal-title":"Autophagy"},{"key":"7515_CR14","doi-asserted-by":"crossref","first-page":"e13298","DOI":"10.1111\/acel.13298","volume":"20","author":"Z Sun","year":"2021","unstructured":"Sun Z, Wang H, Wang Y et al (2021) MiR-103-3p targets the m6 A methyltransferase METTL14 to inhibit osteoblastic bone formation. Aging Cell 20:e13298","journal-title":"Aging Cell"},{"key":"7515_CR15","doi-asserted-by":"publisher","first-page":"3515","DOI":"10.1002\/jcp.26203","volume":"233","author":"F de Toledo Frias","year":"2017","unstructured":"de Toledo Frias F, Rocha KCE, de Mendon\u00e7a M et al (2017) Fenofibrate reverses changes induced by high-fat diet on metabolism in mice muscle and visceral adipocytes. J Cell Physiol 233:3515\u20133528","journal-title":"J Cell Physiol"},{"key":"7515_CR16","doi-asserted-by":"publisher","first-page":"723","DOI":"10.18821\/0869-2084-2019-64-12-723-729","volume":"64","author":"PP Gimadiev","year":"2019","unstructured":"Gimadiev PP, Niiazov AR (2019) The diagnostic importance of circulating microRNA for non-alcoholic fatty liver disease (review of literature). Klin Lab Diagn 64:723\u2013729","journal-title":"Klin Lab Diagn"},{"key":"7515_CR17","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.omtn.2016.11.005","volume":"6","author":"JH Kim","year":"2017","unstructured":"Kim JH, Lee BR, Choi ES et al (2017) Reverse expression of aging-associated molecules through transfection of miRNAs to aged mice. Mol Ther Nucleic Acids 6:106\u2013115","journal-title":"Mol Ther Nucleic Acids"},{"key":"7515_CR18","doi-asserted-by":"publisher","first-page":"3313","DOI":"10.1007\/s00018-018-2860-6","volume":"75","author":"DH Ipsen","year":"2018","unstructured":"Ipsen DH, Lykkesfeldt J, Tveden-Nyborg P (2018) Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease. Cell Mol Life Sci 75:3313\u20133327","journal-title":"Cell Mol Life Sci"},{"key":"7515_CR19","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1038\/s41575-019-0212-0","volume":"17","author":"M Eslam","year":"2019","unstructured":"Eslam M, George J (2019) Genetic contributions to NAFLD: leveraging shared genetics to uncover systems biology. Nat Rev Gastroenterol Hepatol 17:40\u201352","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"7515_CR20","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1038\/s41575-019-0169-z","volume":"16","author":"V Nobili","year":"2019","unstructured":"Nobili V, Alisi A, Valenti L et al (2019) NAFLD in children: new genes, new diagnostic modalities and new drugs. Nat Rev Gastroenterol Hepatol 16:517\u2013530","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"7515_CR21","doi-asserted-by":"publisher","first-page":"527059","DOI":"10.3389\/fmed.2020.527059","volume":"7","author":"AR L\u00f3pez-Pastor","year":"2020","unstructured":"L\u00f3pez-Pastor AR, Infante-Men\u00e9ndez J, Escribano \u00d3 et al (2020) miRNA Dysregulation in the development of non-alcoholic fatty liver disease and the related disorders type 2 diabetes mellitus and cardiovascular disease. Front Med (Lausanne) 7:527059","journal-title":"Front Med (Lausanne)"},{"key":"7515_CR22","doi-asserted-by":"publisher","first-page":"2890","DOI":"10.3390\/nu11122890","volume":"11","author":"M Oses","year":"2019","unstructured":"Oses M, Margareto Sanchez J, Portillo MP et al (2019) Circulating miRNAs as biomarkers of obesity and obesity-associated comorbidities in children and adolescents: a systematic review. Nutrients 11:2890","journal-title":"Nutrients"},{"key":"7515_CR23","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1016\/j.jhep.2019.05.008","volume":"71","author":"GN Ioannou","year":"2019","unstructured":"Ioannou GN, Green P, Kerr KF et al (2019) Models estimating risk of hepatocellular carcinoma in patients with alcohol or NAFLD-related cirrhosis for risk stratification. J Hepatol 71:523\u2013533","journal-title":"J Hepatol"},{"key":"7515_CR24","doi-asserted-by":"publisher","first-page":"2877","DOI":"10.1111\/bph.14713","volume":"176","author":"Y Rao","year":"2019","unstructured":"Rao Y, Lu YT, Li C et al (2019) Bouchardatine analogue alleviates NAFLD\/NASH in high fat fed mice via blunting ATP synthase activity. Br J Pharmacol 176:2877\u20132893","journal-title":"Br J Pharmacol"},{"key":"7515_CR25","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.cld.2015.10.007","volume":"20","author":"PD Berk","year":"2016","unstructured":"Berk PD, Verna EC (2016) Nonalcoholic fatty liver disease: lipids and insulin resistance. Clin Liver Dis 20:245\u2013262","journal-title":"Clin Liver Dis"},{"key":"7515_CR26","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.bcp.2018.07.005","volume":"155","author":"AD Quiroga","year":"2018","unstructured":"Quiroga AD, Lehner R (2018) Pharmacological intervention of liver triacylglycerol lipolysis: The good, the bad and the ugly. Biochem Pharmacol 155:233\u2013241","journal-title":"Biochem Pharmacol"},{"key":"7515_CR27","doi-asserted-by":"publisher","first-page":"1352","DOI":"10.2337\/dc19-1892","volume":"43","author":"ML Hartman","year":"2020","unstructured":"Hartman ML, Sanyal AJ, Loomba R et al (2020) Effects of novel dual GIP and GLP-1 receptor agonist tirzepatide on biomarkers of nonalcoholic steatohepatitis in patients with type 2 diabetes. Diabetes Care 43:1352\u20131355","journal-title":"Diabetes Care"},{"key":"7515_CR28","doi-asserted-by":"publisher","first-page":"101134","DOI":"10.1016\/j.molmet.2020.101134","volume":"50","author":"M Shum","year":"2021","unstructured":"Shum M, Ngo J, Shirihai OS et al (2021) Mitochondrial oxidative function in NAFLD: friend or foe? Mol Metab 50:101134","journal-title":"Mol Metab"},{"key":"7515_CR29","doi-asserted-by":"publisher","first-page":"911","DOI":"10.3390\/ijms19030911","volume":"19","author":"JA Del Campo","year":"2018","unstructured":"Del Campo JA, Gallego-Dur\u00e1n R, Gallego P et al (2018) Genetic and epigenetic regulation in nonalcoholic fatty liver disease (NAFLD). Int J Mol Sci 19:911","journal-title":"Int J Mol Sci"},{"key":"7515_CR30","doi-asserted-by":"publisher","first-page":"6167","DOI":"10.1111\/jcmm.13902","volume":"22","author":"D Ye","year":"2018","unstructured":"Ye D, Lou G, Zhang T et al (2018) MiR-17 family-mediated regulation of Pknox1 influences hepatic steatosis and insulin signaling. J Cell Mol Med 22:6167\u20136175","journal-title":"J Cell Mol Med"},{"key":"7515_CR31","doi-asserted-by":"publisher","first-page":"E34","DOI":"10.1152\/ajpendo.00528.2019","volume":"319","author":"X Liu","year":"2020","unstructured":"Liu X, Chen S, Zhang L (2020) Downregulated microRNA-130b-5p prevents lipid accumulation and insulin resistance in a murine model of nonalcoholic fatty liver disease. Am J Physiol Endocrinol Metab 319:E34\u2013E42","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"7515_CR32","doi-asserted-by":"publisher","first-page":"119011","DOI":"10.1016\/j.lfs.2020.119011","volume":"268","author":"X Zhou","year":"2021","unstructured":"Zhou X, Yuan Y, Teng F et al (2021) Obesity-induced upregulation of microRNA-183-5p promotes hepatic triglyceride accumulation by targeting the B-cell translocation gene 1. Life Sci 268:119011","journal-title":"Life Sci"},{"key":"7515_CR33","doi-asserted-by":"publisher","first-page":"113011","DOI":"10.1016\/j.ecoenv.2021.113011","volume":"228","author":"C Li","year":"2021","unstructured":"Li C, Jiang L, Jin Y et al (2021) Lipid metabolism disorders effects of 6:2 chlorinated polyfluorinated ether sulfonate through Hsa-miRNA-532-3p\/Acyl-CoA oxidase 1(ACOX1) pathway. Ecotoxicol Environ Saf 228:113011","journal-title":"Ecotoxicol Environ Saf"},{"key":"7515_CR34","doi-asserted-by":"publisher","first-page":"3825","DOI":"10.1096\/fj.201802015R","volume":"33","author":"S Kumar","year":"2019","unstructured":"Kumar S, Rani R, Karns R et al (2019) Augmenter of liver regeneration protein deficiency promotes hepatic steatosis by inducing oxidative stress and microRNA-540 expression. FASEB J 33:3825\u20133840","journal-title":"FASEB J"},{"key":"7515_CR35","doi-asserted-by":"publisher","first-page":"486","DOI":"10.7150\/thno.22059","volume":"8","author":"YH Lai","year":"2018","unstructured":"Lai YH, Liu H, Chiang WF et al (2018) MiR-31-5p-ACOX1 axis enhances tumorigenic fitness in oral squamous cell carcinoma via the promigratory prostaglandin E2. Theranostics 8:486\u2013504","journal-title":"Theranostics"},{"key":"7515_CR36","doi-asserted-by":"publisher","first-page":"104681","DOI":"10.1016\/j.meegid.2020.104681","volume":"89","author":"Y Li","year":"2020","unstructured":"Li Y, Zhu H, Pan L et al (2020) microRNA-103a-3p confers protection against lipopolysaccharide-induced sepsis and consequent multiple organ dysfunction syndrome by targeting HMGB1. Infect Genet Evol 89:104681","journal-title":"Infect Genet Evol"}],"container-title":["Molecular Biology Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11033-022-07515-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11033-022-07515-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11033-022-07515-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T02:48:03Z","timestamp":1700621283000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11033-022-07515-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,23]]},"references-count":36,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["7515"],"URL":"https:\/\/doi.org\/10.1007\/s11033-022-07515-w","relation":{},"ISSN":["0301-4851","1573-4978"],"issn-type":[{"value":"0301-4851","type":"print"},{"value":"1573-4978","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,23]]},"assertion":[{"value":"21 February 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 April 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 May 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare there are no competing interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All experiments were conducted according to the guidelines of Zhejiang University.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}