{"doi":"10.1007/s10571-024-01455-8","title":"Roles of HOTAIR Long Non-coding RNA in Gliomas and Other CNS Disorders","abstract":"<jats:title>Abstract</jats:title><jats:p>HOX transcript antisense intergenic RNA (<jats:italic>HOTAIR</jats:italic>) is a long non-coding RNA (lncRNA) which is increasingly being perceived as a tremendous molecular mediator of brain pathophysiology at multiple levels. Epigenetic regulation of target gene expression carried out by <jats:italic>HOTAIR</jats:italic> is thorough modulation of chromatin modifiers; histone methyltransferase polycomb repressive complex 2 (PRC2) and histone demethylase lysine-specific demethylase 1 (LSD1). Incidentally, <jats:italic>HOTAIR</jats:italic> was the first lncRNA shown to elicit sponging of specific microRNA (miRNA or miR) species in a trans-acting manner. It has been extensively studied in various cancers, including gliomas and is regarded as a prominent pro-tumorigenic and pro-oncogenic lncRNA. Indeed, the expression of <jats:italic>HOTAIR</jats:italic> may serve as glioma grade predictor and prognostic biomarker. The objective of this timely review is not only to outline the multifaceted pathogenic roles of <jats:italic>HOTAIR</jats:italic> in the development and pathophysiology of gliomas and brain cancers, but also to delineate the research findings implicating it as a critical regulator of overall brain pathophysiology. While the major focus is on neuro-oncology, wherein <jats:italic>HOTAIR</jats:italic> represents a particularly potent underlying pathogenic player and a suitable therapeutic target, mechanisms underlying the regulatory actions of <jats:italic>HOTAIR</jats:italic> in neurodegeneration, traumatic, hypoxic and ischemic brain injuries, and neuropsychiatric disorders are also presented.</jats:p>\n                <jats:p><jats:bold>Graphical Abstract</jats:bold></jats:p>\n                <jats:p>HOTAIR-mediated epigenetic DNA regulation and molecular sponging of target miRNAs. While the 5′ end of HOTAIR regulates the H3K27 trimethylation activity of the catalytic subunit enhancer of Zeste homolog 2 (EZH2) of the polycomb repressive complex 2 (PRC2), its 3′ end modulates the H3K4 demethylation activity of lysine-specific demethylase 1 (LSD1). HOTAIR also binds to and competitively inhibits the functions of target miRNAs, altering the expression of downstream genes.\n</jats:p>","journal":"Cellular and Molecular Neurobiology","year":2024,"id":45340,"datarank":0.7193660609547654,"base_score":3.1354942159291497,"endowment":3.1354942159291497,"self_citation_contribution":0.47032413238937254,"citation_network_contribution":0.2490419285653929,"self_endowment_contribution":0.47032413238937254,"citer_contribution":0.2490419285653929,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":22,"citers_with_citation_signal":17,"citers_with_endowment":17,"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":211936,"name":"Ravi Sudesh","orcid":null,"position":1,"is_corresponding":false},{"id":211937,"name":"A. Toufeeq Ahmed","orcid":null,"position":2,"is_corresponding":false},{"id":211938,"name":"Shafiul Haque","orcid":null,"position":3,"is_corresponding":false},{"id":211935,"name":"Faraz Ahmad","orcid":"0000-0003-4284-8045","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.1354942159291497,"endowment":3.1354942159291497,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"38366205","pmcid":"PMC10873238","openalex_id":"https://openalex.org/W4391876830","authors":[],"funders":[{"funder_name":"Deputyship for Research & Innovation, Ministry of Education in Saudi Arabia","grant_id":"Project Number ISP23-101","title":null}],"total_grants":1,"fwci":5.5479,"citation_percentile":0.96604607,"influential_citations":0,"citation_trend":[{"year":2024,"count":7},{"year":2025,"count":12},{"year":2026,"count":3}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://link.springer.com/content/pdf/10.1007/s10571-024-01455-8.pdf","host_type":"journal"},{"url":"https://link.springer.com/content/pdf/10.1007/s10571-024-01455-8.pdf","host_type":"publisher"},{"url":"https://link.springer.com/article/10.1007/s10571-024-01455-8/fulltext.html","host_type":"publisher"},{"url":"https://doi.org/10.1007/s10571-024-01455-8","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/38366205","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10873238","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10873238/pdf/10571_2024_Article_1455.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC10873238","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC10873238?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Cancer-related molecular mechanisms research","Circular RNAs in diseases","RNA modifications and cancer","Medicine","Biology","Humans","Central Nervous System Diseases","Epigenesis, Genetic","Gene Expression Regulation, Neoplastic","Glioma","MicroRNAs","Polycomb Repressive Complex 2","RNA, Long Noncoding"],"mesh_terms":["Central Nervous System Diseases","Glioma","Humans","Gene Expression Regulation, Neoplastic","MicroRNAs","Epigenesis, Genetic","RNA, Long Noncoding","Polycomb Repressive Complex 2"],"keywords":["HOTAIR","PRC2","Long non-coding RNA","Demethylase","EZH2","Biology","Epigenetics","microRNA","Competing endogenous RNA","Cancer research","Hox gene","Histone","Chromatin","Non-coding RNA","Histone H3","Gene expression","RNA","Genetics","Gene","Traumatic brain injury","Brain cancer","Alzheimer’s disease","Parkinson’s Disease","Neuropsychiatric Diseases","Sponging"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"refsnp"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-03T00:39:31.037999Z","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":[]}