{"doi":"10.17615/e43w-p608","title":"miR-17 92 cooperates with RB pathway mutations to promote retinoblastoma","abstract":"The miR-17∼92 cluster is a potent microRNA-encoding oncogene. Here, we show that miR-17∼92 synergizes with loss of Rb family members to promote retinoblastoma. We observed miR-17∼92 genomic amplifications in murine retinoblastoma and high expression of miR-17∼92 in human retinoblastoma. While miR-17∼92 was dispensable for mouse retinal development, miR-17∼92 overexpression, together with deletion of Rb and p107, led to rapid emergence of retinoblastoma with frequent metastasis to the brain. miR-17∼92 oncogenic function in retinoblastoma was not mediated by a miR-19/PTEN axis toward apoptosis suppression, as found in lymphoma/leukemia models. Instead, miR-17∼92 increased the proliferative capacity of Rb/p107-deficient retinal cells. We found that deletion of Rb family members led to compensatory up-regulation of the cyclin-dependent kinase inhibitor p21Cip1. miR-17∼92 overexpression counteracted p21Cip1 up-regulation, promoted proliferation, and drove retinoblastoma formation. These results demonstrate that the oncogenic determinants of miR-17∼92 are context-specific and provide new insights into miR-17∼92 function as an RB-collaborating gene in cancer.","journal":"UNC Libraries","year":2020,"id":121911,"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":0.9537,"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":562638,"name":"K. Conkrite","orcid":null,"position":1,"is_corresponding":false},{"id":393791,"name":"S. M. Hammond","orcid":null,"position":2,"is_corresponding":false},{"id":562639,"name":"M. Sundby","orcid":null,"position":3,"is_corresponding":false},{"id":562640,"name":"D‐K Mu","orcid":null,"position":4,"is_corresponding":false},{"id":357096,"name":"J. M. Thomson","orcid":null,"position":5,"is_corresponding":false},{"id":562641,"name":"S. Mukai","orcid":null,"position":6,"is_corresponding":false},{"id":562637,"name":"D. MacPherson","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:14:46.979435Z","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":[]}