{"doi":"10.1093/hmg/ddab187","title":"The SWI/SNF complex regulates the expression of miR-222, a tumor suppressor microRNA in lung adenocarcinoma","abstract":"SWitch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complexes are key epigenetic regulators that are recurrently mutated in cancer. Most studies of these complexes are focused on their role in regulating protein-coding genes. However, here, we show that SWI/SNF complexes control the expression of microRNAs. We used a SMARCA4-deficient model of lung adenocarcinoma (LUAD) to track changes in the miRNome upon SMARCA4 restoration. We found that SMARCA4-SWI/SNF complexes induced significant changes in the expression of cancer-related microRNAs. The most significantly dysregulated microRNA was miR-222, whose expression was promoted by SMARCA4-SWI/SNF complexes, but not by SMARCA2-SWI/SNF complexes via their direct binding to a miR-222 enhancer region. Importantly, miR-222 expression decreased cell viability, phenocopying the tumor suppressor role of SMARCA4-SWI/SNF complexes in LUAD. Finally, we showed that the miR-222 enhancer region resides in a topologically associating domain that does not contain any cancer-related protein-coding genes, suggesting that miR-222 may be involved in exerting the tumor suppressor role of SMARCA4. Overall, this study highlights the relevant role of the SWI/SNF complex in regulating the non-coding genome, opening new insights into the pathogenesis of LUAD.","journal":"Human Molecular Genetics","year":2021,"id":185988,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9533,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":355618,"name":"Álvaro Andrades","orcid":"0000-0001-9042-8964","position":1,"is_corresponding":false},{"id":642991,"name":"Jordi Martorell‐Marugán","orcid":"0000-0002-5186-0735","position":2,"is_corresponding":false},{"id":694358,"name":"Jeffrey R. Haswell","orcid":null,"position":3,"is_corresponding":false},{"id":395013,"name":"Frank J. Slack","orcid":"0000-0001-8263-0409","position":4,"is_corresponding":false},{"id":642988,"name":"Pedro Carmona‐Sáez","orcid":"0000-0002-6173-7255","position":5,"is_corresponding":false},{"id":355625,"name":"Pedro P. Medina","orcid":"0000-0002-7834-7093","position":6,"is_corresponding":false},{"id":693601,"name":"Paola Peinado","orcid":"0000-0003-2484-928X","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-18T23:48:42.632147Z","pmid":"34240140","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":[]}