{"doi":"10.1101/2023.01.30.526369","title":"Pan-Cancer Biomarker miR-151a Regulates p21 Partially Through p53","abstract":"ABSTRACT Dysregulation of microRNAs (miRNAs) has been associated with a variety of cancers. We previously identified miR-151a as a potential cell fitness-regulating microRNA using a miRNA-targeted CRISPR-Cas9 genetic screen. In this study, we created mutant cell clones with loss of miR-151a expression and verified miR-151a mutations indeed decreased cell growth. In miR-151a mutant cells, there was an increase in the fraction of cells in the G1-phase of the cell cycle. This increase in G1 cells corresponded to an increase in p53 (TP53) and p21 (CDKN1A) protein levels. Both strands of miR-151a could suppress p53; miR-151a-3p was able to directly suppress p53 expression, but the miR-151a-5p suppression of p53 apparently was indirect. Re-expression of miR-151a-5p in the mutant cells significantly decreased the p53 and p21 protein levels as well as the percentage of cells in G1, while re-expression of miR-151a-3p ironically had a modest effect. These results suggest that both the 5p and 3p strands as well as additional factors are involved in the regulation of p53/p21 and the cell cycle by miR-151a. We also analyzed the TCGA database and discovered that increased miR-151a expression occurs in many tumor types; furthermore, there was an inverse correlation between miR-151a and p21 expression, and high miR-151a expression was often associated with poor overall survival. Taken together, results from this study identify a previously underappreciated role of miR-151a in cancer through regulation of the cell cycle, and they also suggest inhibiting the less abundant 5p may be more important than inhibiting the more abundant 3p of miR-151a for therapeutic considerations.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":394108,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9539,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":505236,"name":"Ren-Jang Lin","orcid":"0000-0002-2738-2438","position":1,"is_corresponding":false},{"id":1168517,"name":"Jessica Kurata","orcid":"0000-0003-2624-9413","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T01:19:10.334330Z","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":[]}