{"doi":"10.3390/ijms23052657","title":"DNA Hydroxymethylation in Smoking-Associated Cancers","abstract":"5-hydroxymethylcytosine (5-hmC) was first detected in mammalian DNA five decades ago. However, it did not take center stage in the field of epigenetics until 2009, when ten-eleven translocation 1 (TET1) was found to oxidize 5-methylcytosine to 5-hmC, thus offering a long-awaited mechanism for active DNA demethylation. Since then, a remarkable body of research has implicated DNA hydroxymethylation in pluripotency, differentiation, neural system development, aging, and pathogenesis of numerous diseases, especially cancer. Here, we focus on DNA hydroxymethylation in smoking-associated carcinogenesis to highlight the diagnostic, therapeutic, and prognostic potentials of this epigenetic mark. We describe the significance of 5-hmC in DNA demethylation, the importance of substrates and cofactors in TET-mediated DNA hydroxymethylation, the regulation of TETs and related genes (isocitrate dehydrogenases, fumarate hydratase, and succinate dehydrogenase), the cell-type dependency and genomic distribution of 5-hmC, and the functional role of 5-hmC in the epigenetic regulation of transcription. We showcase examples of studies on three major smoking-associated cancers, including lung, bladder, and colorectal cancers, to summarize the current state of knowledge, outstanding questions, and future direction in the field.","journal":"International Journal of Molecular Sciences","year":2022,"id":251669,"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":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9505,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":895098,"name":"Amanda Caceres","orcid":"0000-0001-8706-7547","position":1,"is_corresponding":false},{"id":321541,"name":"Stella Tommasi","orcid":"0000-0001-6897-4985","position":2,"is_corresponding":false},{"id":321540,"name":"Ahmad Besaratinia","orcid":"0000-0001-7231-228X","position":0,"is_corresponding":true}],"reference_count":225,"raw_metadata":null,"created_at":"2026-07-19T00:24:41.993282Z","pmid":"35269796","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":[]}