{"doi":"10.1042/bcj20240626","title":"The PRL2 phosphatase up-regulates miR-21 through activation of the JAK2/STAT3 pathway to down-regulate the PTEN tumor suppressor","abstract":"The phosphatases of regenerating liver (PRLs) are members of the protein tyrosine phosphatase (PTP) superfamily that play pro-oncogenic roles in cell proliferation, migration, and survival. We previously demonstrated that PRLs can post-translationally down-regulate PTEN, a tumor suppressor frequently inactivated in human cancers, by dephosphorylating PTEN at Tyr336, which promotes the NEDD4-mediated PTEN ubiquitination and proteasomal degradation. Here, we report that PRLs can also reduce PTEN expression by up-regulating microRNA-21 (miR-21), which is one of the most frequently overexpressed miRNAs in solid tumors. We observe a broad correlation between PRL and miR-21 levels in multiple human cancers. Mechanistically, PRL2, the most abundant and ubiquitously expressed PRL family member, promotes the JAK2/STAT3 pathway-mediated miR-21 expression by directly dephosphorylating JAK2 at Tyr570. Finally, we confirm that the PRL2-mediated miR-21 expression contributes to its oncogenic potential in breast cancer cells. Our study defines a new functional role of PRL2 in PTEN regulation through a miR-21-dependent post-transcriptional mechanism, in addition to our previously reported NEDD4-dependent post-translational PTEN regulation. Together, these studies further establish the PRLs as negative regulators of PTEN.","journal":"Biochemical Journal","year":2024,"id":451145,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.952,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":662146,"name":"Yunpeng Bai","orcid":"0000-0002-5879-3555","position":1,"is_corresponding":false},{"id":1054474,"name":"Sarah M. Cavender","orcid":null,"position":2,"is_corresponding":false},{"id":1071942,"name":"Yiming Miao","orcid":"0000-0001-6422-1118","position":3,"is_corresponding":false},{"id":913467,"name":"Frederick Nguele Meke","orcid":"0000-0001-8542-0343","position":4,"is_corresponding":false},{"id":1272599,"name":"Emily L. Lasse-Opsahl","orcid":null,"position":5,"is_corresponding":false},{"id":250404,"name":"Peipei Zhu","orcid":"0000-0003-4508-022X","position":6,"is_corresponding":false},{"id":239968,"name":"Gina M. Doody","orcid":"0000-0003-0665-6759","position":7,"is_corresponding":false},{"id":250410,"name":"W. Andy Tao","orcid":"0000-0002-5535-5517","position":8,"is_corresponding":false},{"id":341920,"name":"Zhong-Yin Zhang","orcid":"0000-0001-5527-7910","position":9,"is_corresponding":false},{"id":1125296,"name":"Qinglin Li","orcid":"0000-0002-4125-1944","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-19T02:02:41.417944Z","pmid":"39665584","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":[]}