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The results of the present study show that the BRD4 inhibitor JQ1 promotes the apoptosis of B16 melanoma cells by altering mitochondrial dynamics, thereby inducing mitochondrial dysfunction and increasing oxidative stress. We found that treatment of B16 cells with different concentrations of JQ1 (125\u00a0nmol\/L or 250\u00a0nmol\/L) significantly downregulated the expression of protein subunits involved in mitochondrial respiratory chain complexes I, III, IV, and V, increased reactive oxygen species, induced energy metabolism dysfunction, significantly enhanced apoptosis, and activated the mitochondrial apoptosis pathway. At the same time, JQ1 inhibited the activation of AMP\u2010activated protein kinase, a metabolic energy sensor. In addition, we found that the mRNA and protein levels of mitochondrial dynamin\u2010related protein 1 increased, whereas the levels of mitochondrial fusion protein 1 and optic atrophy protein 1 decreased. Mechanistically, we determined that JQ1 inhibited the expression of c\u2010Myc and altered mitochondrial dynamics, eventually leading to changes in the mitochondrial function, metabolism, and apoptosis of B16 melanoma cells.<\/jats:p>","DOI":"10.1111\/cas.15061","type":"journal-article","created":{"date-parts":[[2021,7,12]],"date-time":"2021-07-12T19:05:01Z","timestamp":1626116701000},"page":"4013-4025","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Bromodomain\u2010containing protein 4 inhibitor JQ1 promotes melanoma cell apoptosis by regulating mitochondrial dynamics"],"prefix":"10.1111","volume":"112","author":[{"given":"Liyuan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery China\u2010Japan Union Hospital Jilin University Changchun China"},{"name":"Department of Pathophysiology Prostate Diseases Prevention and Treatment Research Center College of Basic Medical Science Jilin University Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology Prostate Diseases Prevention and Treatment Research Center College of Basic Medical Science Jilin University Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology Prostate Diseases Prevention and Treatment Research Center College of Basic Medical Science Jilin University Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology Prostate Diseases Prevention and Treatment Research Center College of Basic Medical Science Jilin University Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9205-5217","authenticated-orcid":false,"given":"Yuxin","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery China\u2010Japan Union Hospital Jilin University Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25019"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R700001200"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09504"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx157"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.08.017"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2015.196"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102339"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.05.004"},{"key":"e_1_2_7_10_1","doi-asserted-by":"crossref","unstructured":"LabartaE deLos SantosMJ Escrib\u00e1MJ PellicerA HerraizS. 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