{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Li X"],"funding":["Guangdong Provincial Key Laboratory of Construction Foundation","Guangdong Basic and Applied Basic Research Foundation","Natural Science Foundation of Guangdong Province","National Natural Science Foundation of China"],"pagination":["8255-8268"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7470982"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["48(15)"],"pubmed_abstract":["Nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) are global epidemic public health problems with pathogenesis incompletely understood. Hepatocyte excessive apoptosis is a significant symbol for NAFLD/NASH patients, and therefore anti-apoptosis therapy could be used for NAFLD/NASH treatment. Up-regulation of BCL-2 has been found to be closely related with anti-apoptosis. BCL-2 gene promoter region has a C-rich sequence, which can form i-motif structure and play important role in regulating gene transcription. In this study, after extensive screening and evaluation, we found that acridone derivative A22 could up-regulate BCL-2 transcription and translation in vitro and in cells through selective binding to and stabilizing BCL-2 gene promoter i-motif. Our further experiments showed that A22 could reduce hepatocyte apoptosis in NAFLD/NASH model possibly through up-regulating BCL-2 expression. A22 could reduce inflammation, endoplasmic reticulum stress and cirrhosis in high-fat diet-fed mice liver model. Our findings provide a potentially new approach of anti-apoptosis for NAFLD/NASH treatment, and A22 could be further developed as a lead compound for NAFLD/NASH therapy. Our present study first demonstrated that gene promoter i-motif could be targeted for gene up-regulation for extended treatment of other important diseases besides cancer."],"journal":["Nucleic acids research"],"pubmed_title":["Upregulation of BCL-2 by acridone derivative through gene promoter i-motif for alleviating liver damage of NAFLD/NASH."],"pmcid":["PMC7470982"],"funding_grant_id":["2019A1515011074","2017A030313089","2017B030314030","2017A030308003","21977123"],"pubmed_authors":["Shu B","Li X","Li D","Kang S","Zhang M","Wei Z","Wang J","Huang ZS","Gong X"],"additional_accession":[]},"is_claimable":false,"name":"Upregulation of BCL-2 by acridone derivative through gene promoter i-motif for alleviating liver damage of NAFLD/NASH.","description":"Nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) are global epidemic public health problems with pathogenesis incompletely understood. Hepatocyte excessive apoptosis is a significant symbol for NAFLD/NASH patients, and therefore anti-apoptosis therapy could be used for NAFLD/NASH treatment. Up-regulation of BCL-2 has been found to be closely related with anti-apoptosis. BCL-2 gene promoter region has a C-rich sequence, which can form i-motif structure and play important role in regulating gene transcription. In this study, after extensive screening and evaluation, we found that acridone derivative A22 could up-regulate BCL-2 transcription and translation in vitro and in cells through selective binding to and stabilizing BCL-2 gene promoter i-motif. Our further experiments showed that A22 could reduce hepatocyte apoptosis in NAFLD/NASH model possibly through up-regulating BCL-2 expression. A22 could reduce inflammation, endoplasmic reticulum stress and cirrhosis in high-fat diet-fed mice liver model. Our findings provide a potentially new approach of anti-apoptosis for NAFLD/NASH treatment, and A22 could be further developed as a lead compound for NAFLD/NASH therapy. Our present study first demonstrated that gene promoter i-motif could be targeted for gene up-regulation for extended treatment of other important diseases besides cancer.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Sep","modification":"2026-05-07T16:15:03.649Z","creation":"2020-09-12T07:06:19Z"},"accession":"S-EPMC7470982","cross_references":{"pubmed":["32710621"],"doi":["10.1093/nar/gkaa615"]}}