{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:05:04Z","timestamp":1790373904868,"version":"4.1.0"},"reference-count":31,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,3,28]],"date-time":"2020-03-28T00:00:00Z","timestamp":1585353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1C1C1005423"],"award-info":[{"award-number":["2020R1C1C1005423"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2016M3C7A1905074"],"award-info":[{"award-number":["2016M3C7A1905074"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2016R1A2B4009409"],"award-info":[{"award-number":["2016R1A2B4009409"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017R1D1A1B03028839"],"award-info":[{"award-number":["2017R1D1A1B03028839"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Several studies have shown that brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1 (BMAL1), an important molecule for maintaining circadian rhythms, inhibits the growth and metastasis of tumor cells in several types of cancer, including lung, colon, and breast cancer. However, its role in glioblastoma has not yet been established. Here, we addressed the function of BMAL1 in U87MG glioblastoma cells with two approaches\u2014loss and gain of function. In the loss of function experiments, cell proliferation in U87MG cells transfected with small interfering RNA (siRNA) targeting BMAL1 was increased by approximately 24% (small interfering (si)-NC 0.91 \u00b1 0.00 vs. si-BMAL1 1.129 \u00b1 0.08) via upregulation of cyclin B1. In addition, cell migration and invasion of BMAL1 siRNA-treated glioblastoma cells were elevated by approximately 20% (si-NC 51.00 \u00b1 1.53 vs. si-BMAL161.33 \u00b1 0.88) and 209% (si-NC 21.28 \u00b1 1.37 vs. si-BMAL1 44.47 \u00b1 3.48), respectively, through the accumulation of phosphorylated-AKT (p-AKT) and matrix metalloproteinase (MMP)-9. Gain of function experiments revealed that adenovirus-mediated ectopic expression of BMAL1 in U87MG cells resulted in a 19% (Adenovirus (Ad)-vector 0.94\u00b1 0.03 vs. Ad-BMAL1 0.76 \u00b1 0.03) decrease in cell proliferation compared with the control via downregulation of cyclin B1 and increased early and late apoptosis due to changes in the levels of BCL2-associated X protein (BAX), B-cell lymphoma 2 (BCL-2), and cleaved caspase-3. Likewise, cell migration and invasion were attenuated by approximately 24% (Ad-vector 55.00 \u00b1 0.00 vs. Ad-BMAL1 41.83 \u00b1 2.90) and 49% (Ad-vector 70.01 \u00b1 1.24 vs. Ad-BMAL1 35.55 \u00b1 1.78), respectively, in BMAL1-overexpressing U87MG cells following downregulation of p-AKT and MMP-9. Taken together, our results suggest that BMAL1 acts as an anti-cancer gene by altering the proliferation, migration, and invasion of glioblastoma cells. Therefore, the BMAL1 gene could be a potential therapeutic target in the treatment of glioblastoma.<\/jats:p>","DOI":"10.3390\/ijms21072352","type":"journal-article","created":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T03:44:13Z","timestamp":1585712653000},"page":"2352","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["BMAL1 Suppresses Proliferation, Migration, and Invasion of U87MG Cells by Downregulating Cyclin B1, Phospho-AKT, and Metalloproteinase-9"],"prefix":"10.3390","volume":"21","author":[{"given":"Do hyeong","family":"Gwon","sequence":"first","affiliation":[{"name":"Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, Korea"},{"name":"Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo-Yong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Regional Rheumatoid and Degenerative Arthritis Center, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3122-9417","authenticated-orcid":false,"given":"Nara","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, Korea"},{"name":"Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song I","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, Korea"},{"name":"Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuhee","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Pain Medicine, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won-hyung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Pain Medicine, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7691-1394","authenticated-orcid":false,"given":"Dong Woon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, Korea"},{"name":"Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4776-4396","authenticated-orcid":false,"given":"Jinpyo","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Physiology, and Dental Research Institute, School of Dentistry, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6124-5138","authenticated-orcid":false,"given":"Sun Yeul","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Pain Medicine, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e273","DOI":"10.3747\/co.22.2436","article-title":"Nonsurgical treatment of recurrent glioblastoma","volume":"22","author":"Gallego","year":"2015","journal-title":"Curr. 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