{"doi":"10.1124/mol.118.112235","title":"A Transcriptional Regulatory Network Containing Nuclear Receptors and Long Noncoding RNAs Controls Basal and Drug-Induced Expression of Cytochrome P450s in HepaRG Cells","abstract":null,"journal":"Molecular Pharmacology","year":2018,"id":628239,"datarank":0.6038027536102726,"base_score":4.02535169073515,"endowment":4.02535169073515,"self_citation_contribution":0.6038027536102726,"citation_network_contribution":0.0,"self_endowment_contribution":0.6038027536102726,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":55,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":329699,"name":"Yifan Bao","orcid":"0000-0003-0460-9326","position":1,"is_corresponding":false},{"id":1626475,"name":"Stephanie C. Piekos","orcid":null,"position":2,"is_corresponding":false},{"id":1116060,"name":"Kexin Zhu","orcid":"0000-0002-8892-4077","position":3,"is_corresponding":false},{"id":95595,"name":"Lirong Zhang","orcid":"0000-0002-5020-957X","position":4,"is_corresponding":false},{"id":1626476,"name":"Xiao-bo Zhong","orcid":null,"position":5,"is_corresponding":false},{"id":1369608,"name":"Liming Chen","orcid":"0000-0001-5297-2176","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"A Transcriptional Regulatory Network Containing Nuclear Receptors and Long Noncoding RNAs Controls Basal and Drug-Induced Expression of Cytochrome P450s in HepaRG Cells","abstract":"Cytochrome P450 (P450) enzymes are responsible for metabolizing drugs. Expression of P450s can directly affect drug metabolism, resulting in various outcomes in therapeutic efficacy and adverse effects. Several nuclear receptors are transcription factors that can regulate expression of P450s at both basal and drug-induced levels. Some long noncoding RNAs (lncRNAs) near a transcription factor are found to participate in the regulatory functions of the transcription factors. The aim of this study is to determine whether there is a transcriptional regulatory network containing nuclear receptors and lncRNAs controlling both basal and drug-induced expression of P450s in HepaRG cells. Small interfering RNAs or small hairpin RNAs were applied to knock down four nuclear receptors [hepatocyte nuclear factor 1<i>α</i> (HNF1<i>α</i>), hepatocyte nuclear factor 4<i>α</i> (HNF4<i>α</i>), pregnane X receptor (PXR), and constitutive androstane receptor (CAR)] as well as two lncRNAs [HNF1<i>α</i> antisense RNA 1 (HNF1<i>α</i>-AS1) and HNF4<i>α</i> antisense RNA 1 (HNF4<i>α</i>-AS1)] in HepaRG cells with or without treatment of phenobarbital or rifampicin. Expression of eight P450 enzymes was examined in both basal and drug-induced levels. CAR and PXR mainly regulated expression of specific P450s. HNF1<i>α</i> and HNF4<i>α</i> affected expression of a wide range of P450s as well as other transcription factors. HNF1<i>α</i> and HNF4<i>α</i> controlled the expression of their neighborhood lncRNAs, HNF1<i>α</i>-AS1 and HNF4<i>α</i>-AS1, respectively. HNF1<i>α</i>-AS1 and HNF4<i>α</i>-AS1 was also involved in the regulation of P450s and transcription factors in diverse manners. Altogether, our study concludes that a transcription regulatory network containing the nuclear receptors and lncRNAs controls both basal and drug-induced expression of P450s in HepaRG cells.","is_dataset_classified":null,"base_score":4.02535169073515,"endowment":4.02535169073515,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"29691280","pmcid":"PMC5988030","openalex_id":"https://openalex.org/W2802048015","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM118367","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01GM118367-02","title":"Short- or long-term impacts of drug exposure at early life on drug metabolism, therapeutic efficacy, and drug-induced toxicity"}],"total_grants":2,"fwci":1.7781,"citation_percentile":0.84083674,"influential_citations":0,"citation_trend":[{"year":2018,"count":2},{"year":2019,"count":7},{"year":2020,"count":11},{"year":2021,"count":6},{"year":2022,"count":7},{"year":2023,"count":5},{"year":2024,"count":8},{"year":2025,"count":9}],"oa_status":"bronze","license":"Elsevier TDM","oa_locations":[{"url":"https://molpharm.aspetjournals.org/content/molpharm/94/1/749.full.pdf","host_type":"journal"},{"url":"https://molpharm.aspetjournals.org/content/molpharm/94/1/749.full.pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0026895X24007879?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0026895X24007879?httpAccept=text/plain","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1124/mol.118.112235","host_type":"publisher"},{"url":"https://doi.org/10.1124/mol.118.112235","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/29691280","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5988030","host_type":"repository"},{"url":"https://dx.doi.org/10.1124/mol.118.112235","host_type":""}],"fields_of_study":["Cancer-related molecular mechanisms research","Pharmacogenetics and Drug Metabolism","RNA Research and Splicing","0301 basic medicine","03 medical and health sciences","Cell Line","Constitutive Androstane Receptor","Cytochrome P-450 Enzyme System","Gene Expression Regulation","Gene Regulatory Networks","Hepatocyte Nuclear Factor 1-alpha","Hepatocyte Nuclear Factor 4","Hepatocytes","Humans","Liver","Phenobarbital","Pregnane X Receptor","RNA, Long Noncoding","Receptors, Cytoplasmic and Nuclear","Rifampin","Transcriptional Activation"],"mesh_terms":["Pregnane X Receptor","Constitutive Androstane Receptor","Cell Line","Cytochrome P-450 Enzyme System","Gene Expression Regulation","Humans","Liver","Phenobarbital","Rifampin","Transcriptional Activation","Receptors, Cytoplasmic and Nuclear","Hepatocytes","Hepatocyte Nuclear Factor 1-alpha","Hepatocyte Nuclear Factor 4","Gene Regulatory Networks","RNA, Long Noncoding"],"keywords":["Pregnane X receptor","Hepatocyte nuclear factor 4","Hepatocyte nuclear factors","Nuclear receptor","Constitutive androstane receptor","Transcription factor","Biology","Cell biology","Gene expression","Gene","Biochemistry","Transcriptional Activation","Receptors, Cytoplasmic and Nuclear","Cell Line","Cytochrome P-450 Enzyme System","Gene Expression Regulation","Liver","Phenobarbital","Hepatocytes","Humans","Gene Regulatory Networks","RNA, Long Noncoding","Hepatocyte Nuclear Factor 1-alpha","Rifampin"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. Good health"},{"sdg_number":13,"sdg_label":"13. Climate action"},{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-05T12:15:25.208065Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}