{"doi":"10.1016/j.envpol.2024.123396","title":"Genomic and epigenetic characterization of the arsenic-induced oncogenic microRNA-21","abstract":"As one of the first identified oncogenic microRNAs, the precise details concerning the transcriptional regulation and function of microRNA-21 (miR-21) are still not completely established. The miR-21 gene is situated on chromosome 17q23.2, positioned at the 3′-UTR of the gene that encodes vacuole membrane protein-1 (VMP1). In this current study, we presented evidence indicating that miR-21 possesses its own gene promoter, which can be found in the intron 10 of the VMP1 gene. Chromatin immunoprecipitation followed by global DNA sequencing (ChIP-seq) revealed the presence of a broad H3K4me3 peak spanning the entire gene body of the primary miR-21 and the existence of super-enhancer clusters in the close proximity to both the miR-21 gene promoter and the transcription termination site in arsenic (As3+)-induced cancer stem-like cells (CSCs) and human induced pluripotent stem cells (hiPSCs). In non-transformed human bronchial epithelial cells (BEAS-2B), As3+ treatment enhanced Nrf2 binding to both the host gene VMP1 of miR-21 and the miR-21 gene. Knockout of Nrf2 inhibited both the basal and As3+-induced expressions of miR-21. Furthermore, the As3+-enhanced Nrf2 peaks in ChIP-seq fully overlap with these super-enhancers enriched with H3K4me1 and H3K27ac in the miR-21 gene, suggesting that Nrf2 may coordinate with other transcription factors through the super-enhancers to regulate the expression of miR-21 in cellular response to As3+. These findings demonstrate the unique genetic and epigenetic characteristics of miR-21 and may provide insights into understanding the novel mechanisms linking environmental As3+ exposure and human cancers.","journal":"Environmental Pollution","year":2024,"id":455238,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9621,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":73948,"name":"Zhuoyue Bi","orcid":"0000-0001-8559-3543","position":1,"is_corresponding":false},{"id":1151234,"name":"Aashna S. Pawar","orcid":null,"position":2,"is_corresponding":false},{"id":665349,"name":"Akimasa Seno","orcid":"0000-0002-9664-9490","position":3,"is_corresponding":false},{"id":73956,"name":"Bandar Almutairy","orcid":null,"position":4,"is_corresponding":false},{"id":733459,"name":"Yao Fu","orcid":"0000-0003-2348-4872","position":5,"is_corresponding":false},{"id":73950,"name":"Yiran Qiu","orcid":"0000-0001-8669-1209","position":6,"is_corresponding":false},{"id":73951,"name":"Wenxuan Zhang","orcid":"0000-0002-2046-3366","position":7,"is_corresponding":false},{"id":1150914,"name":"Ziwei Wang","orcid":"0000-0001-6005-0286","position":8,"is_corresponding":false},{"id":73955,"name":"Chitra Thakur","orcid":"0000-0002-4356-2543","position":9,"is_corresponding":false},{"id":772762,"name":"Hongjuan Cui","orcid":"0000-0003-1178-1570","position":10,"is_corresponding":false},{"id":1279086,"name":"Liqun Yang","orcid":"0000-0001-5801-7890","position":11,"is_corresponding":false},{"id":881650,"name":"Fei Chen","orcid":"0000-0003-0243-2758","position":12,"is_corresponding":false},{"id":73953,"name":"Haoyan Ji","orcid":"0000-0002-3456-6083","position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-19T02:03:17.458329Z","pmid":"38295932","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":[]}