{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T10:58:30Z","timestamp":1755601110566,"version":"3.38.0"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T00:00:00Z","timestamp":1702857600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81202231","82204134"],"award-info":[{"award-number":["81202231","82204134"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515140180","2020A151501204","2020A1515110614"],"award-info":[{"award-number":["2022A1515140180","2020A151501204","2020A1515110614"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Benzene and its metabolite hydroquinone (HQ) are widely used in daily life, and long\u2010term exposure to benzene or HQ can induce acute myeloid leukemia (AML). Circular RNAs (circRNAs) are mostly produced by reverse splicing of gene exon mRNA precursors. The modulation of circRNA expression is connected to leukemia progression; however, the molecular mechanism is still unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>In this study, the cells were divided into four groups: PBS control group (PBS\u2010TK6), TK6 malignantly transformed cells induced by 10.0\u2009\u03bcmol\/L HQ (HQ\u2010TK6), and HQ\u2010TK6 cells treated with 5\u2009\u03bcmol\/L 5\u2010AzaC (DNA methyltransferase inhibitor) for 24\u2009h (HQ\u2009+\u20095\u2010AzaC). HQ\u2010TK6 cells were treated with 200\u2009nmol\/L TSA (histone deacetylation inhibitor) for 24\u2009h (HQ\u2009+\u2009TSA). qRT\u2013PCR was used to identify the differential hsa_circ_401351 expression between the four groups. We further determined the hsa_circ_401351 promoter methylation level with methylation\u2010specific PCR. DNMT1 and DNMT3b were knocked down by CRISPR\/Cas9 to elucidate the specific molecular mechanism of hsa_circ_401351 in HQ\u2010TK6 cells. CCK\u20108 and flow cytometry detected cell proliferation and apoptosis, respectively, after hsa_circ_401351 was overexpressed in HQ\u2010TK6 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with the PBS\u2010TK6 group, the expression of hsa_circ_401351 was found to be lower in the HQ\u2010TK6 group. Nevertheless, treatment with 5\u2010AzaC or TSA increased hsa_circ_401351 expression, with the upregulation being more pronounced in the TSA group. The expression of hsa_circ_401351 in the DNMT1 knockdown group was dramatically increased by 50% compared to that in the control group, and the DNA methylation level of the hsa_circ_401351 promoter region was decreased. When hsa_circ_401351 was overexpressed, HQ\u2010TK6 cell proliferation was significantly slowed after 48\u2009h compared with the control group. Flow cytometry showed that cells were mainly arrested in G1 phase, and apoptosis was significantly enhanced. Similarly, qRT\u2013PCR and Western blot data showed significant reductions in Caspase\u20103 mRNA and protein production, and Bcl\u20102 mRNA levels were also elevated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Overall, our research showed that elevated DNMT1 expression in HQ\u2010TK6 cells increased methylation levels and decreased expression of the hsa_circ_401351 promoter region, limiting its ability to suppress HQ\u2010TK6 cell growth and enhance apoptosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/tox.24089","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T14:53:27Z","timestamp":1702911207000},"page":"2092-2101","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>DNMT1<\/scp> regulates hypermethylation and silences hsa_circ_401351 in hydroquinone\u2010induced malignant <scp>TK6<\/scp> cells"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1629-3106","authenticated-orcid":false,"given":"Yali","family":"Han","sequence":"first","affiliation":[{"name":"Dongguan Key Laboratory of Environmental Medicine, School of Public Health Guangdong Medical University  Dongguan People's Republic of China"},{"name":"Department of Preventive Medicine, School of Public Health Guangdong Medical University  Dongguan People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinxue","family":"Meng","sequence":"additional","affiliation":[{"name":"Dongguan Key Laboratory of Environmental Medicine, School of Public Health Guangdong Medical University  Dongguan People's Republic of China"},{"name":"Department of Preventive Medicine, School of Public Health Guangdong Medical University  Dongguan People's Republic of 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