{"doi":"10.1002/advs.202202572","title":"Co‐Targeting Plk1 and DNMT3a in Advanced Prostate Cancer","abstract":"Because there is no effective treatment for late-stage prostate cancer (PCa) at this moment, identifying novel targets for therapy of advanced PCa is urgently needed. A new network-based systems biology approach, XDeath, is developed to detect crosstalk of signaling pathways associated with PCa progression. This unique integrated network merges gene causal regulation networks and protein-protein interactions to identify novel co-targets for PCa treatment. The results show that polo-like kinase 1 (Plk1) and DNA methyltransferase 3A (DNMT3a)-related signaling pathways are robustly enhanced during PCa progression and together they regulate autophagy as a common death mode. Mechanistically, it is shown that Plk1 phosphorylation of DNMT3a leads to its degradation in mitosis and that DNMT3a represses Plk1 transcription to inhibit autophagy in interphase, suggesting a negative feedback loop between these two proteins. Finally, a combination of the DNMT inhibitor 5-Aza-2'-deoxycytidine (5-Aza) with inhibition of Plk1 suppresses PCa synergistically.","journal":"Advanced Science","year":2022,"id":292027,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":948414,"name":"Lijun Cheng","orcid":"0000-0002-8451-1662","position":1,"is_corresponding":false},{"id":747532,"name":"Qiongsi Zhang","orcid":"0000-0002-6234-5034","position":2,"is_corresponding":false},{"id":411938,"name":"Yifan Kong","orcid":"0000-0002-5650-8079","position":3,"is_corresponding":false},{"id":271896,"name":"Daheng He","orcid":"0000-0003-0399-2466","position":4,"is_corresponding":false},{"id":747533,"name":"Kunyu Li","orcid":"0000-0001-6095-3020","position":5,"is_corresponding":false},{"id":324871,"name":"Matthew Rea","orcid":null,"position":6,"is_corresponding":false},{"id":438270,"name":"Jianlin Wang","orcid":"0000-0002-1878-1736","position":7,"is_corresponding":false},{"id":497890,"name":"Ruixin Wang","orcid":"0000-0002-9615-7541","position":8,"is_corresponding":false},{"id":411941,"name":"Jinghui Liu","orcid":"0000-0002-9676-1538","position":9,"is_corresponding":false},{"id":497889,"name":"Zhiguo Li","orcid":"0000-0002-6869-2766","position":10,"is_corresponding":false},{"id":631786,"name":"Chongli Yuan","orcid":"0000-0003-3765-0931","position":11,"is_corresponding":false},{"id":747535,"name":"Enze Liu","orcid":"0000-0003-3162-461X","position":12,"is_corresponding":false},{"id":17129,"name":"Yvonne Fondufe‐Mittendorf","orcid":"0000-0002-2551-9920","position":13,"is_corresponding":false},{"id":12406,"name":"Lang Li","orcid":"0000-0002-0746-1809","position":14,"is_corresponding":false},{"id":723067,"name":"Tao Han","orcid":"0000-0001-7100-3979","position":15,"is_corresponding":false},{"id":975707,"name":"Chi Wang","orcid":"0000-0001-9698-6115","position":16,"is_corresponding":false},{"id":411943,"name":"Xiaoqi Liu","orcid":"0000-0002-6613-1746","position":17,"is_corresponding":false},{"id":497888,"name":"Zhuangzhuang Zhang","orcid":"0000-0003-2578-7375","position":0,"is_corresponding":true}],"reference_count":3,"raw_metadata":null,"created_at":"2026-07-19T00:30:42.221508Z","pmid":"35837804","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":[]}