{"doi":"10.3390/cells9091934","title":"Molecular Genetics and Functional Analysis Implicate CDKN2BAS1-CDKN2B Involvement in POAG Pathogenesis","abstract":"The genes in the 9p21 locus (CDKN2B-AS1 & CDKN2B) are widely associated with Primary open-angle glaucoma (POAG). However, the functional importance of this locus in POAG pathogenesis is still unexplored. This study investigated the role of CDKN2BAS1-CDKN2B axis in POAG. We observed significant association of CDKN2B-AS1 SNP rs4977756 with POAG and its endophenotypic traits (vertical cup-disc ratio (p = 0.033) and central corneal thickness (p = 0.008)) by screening African American POAG cases (n = 1567) and controls (n = 1600). A luciferase reporter assay in Human embryonic kidney 293T (HEK293T) cells revealed that the region surrounding rs4977756 likely serves as a transcriptional repressor. siRNA-mediated knockdown of CDKN2B-AS1 in HEK293T cells and trabecular meshwork (TM) cells resulted in significantly increased expression of CDKN2B, which was also observed in human POAG ocular tissues. Pathway focused qRT-PCR gene expression analysis showed increased cellular senescence, TGFβ signaling and ECM deposition in TM cells after CDKN2B-AS1 suppression. In conclusion, we report that CDKN2B-AS1 may act as a regulator, and it could function by modulating the expression of CDKN2B. In addition, increase in CDKN2B levels due to CDKN2B-AS1 suppression may result in the senescence of trabecular meshwork cells leading to POAG pathogenesis.","journal":"Cells","year":2020,"id":76081,"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":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9685,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":397087,"name":"Ian Danford","orcid":"0000-0003-0192-2181","position":1,"is_corresponding":false},{"id":398529,"name":"Harini V. Gudiseva","orcid":null,"position":2,"is_corresponding":false},{"id":398530,"name":"Lana D. Verkuil","orcid":null,"position":3,"is_corresponding":false},{"id":397088,"name":"Maxwell Pistilli","orcid":"0000-0002-4266-4150","position":4,"is_corresponding":false},{"id":393391,"name":"Sushma Vishwakarma","orcid":"0000-0003-2134-1237","position":5,"is_corresponding":false},{"id":393398,"name":"Inderjeet Kaur","orcid":"0000-0003-3660-5039","position":6,"is_corresponding":false},{"id":397089,"name":"Tarjani Vivek Dave","orcid":"0000-0002-2751-1391","position":7,"is_corresponding":false},{"id":291481,"name":"Joan M. O’Brien","orcid":"0000-0003-4109-2928","position":8,"is_corresponding":false},{"id":354103,"name":"Venkata Ramana Murthy Chavali","orcid":"0000-0003-3439-3490","position":9,"is_corresponding":false},{"id":354104,"name":"Sonika Rathi","orcid":"0000-0003-0484-9952","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-18T21:47:46.469293Z","pmid":"32825664","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":[]}