{"doi":"10.1002/hon.3004","title":"LncRNA FIRRE stimulates PTBP1‐induced Smurf2 decay, stabilizes B‐cell receptor, and promotes the development of diffuse large B‐cell lymphoma","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Sustained expression of B‐cell receptor (BCR) critically contributes to the development of diffuse large B‐cell lymphoma (DLBCL). However, little is known on the mechanism regulating BCR expression. In the present study, we explored the biological significance of functional intergenic repeating RNA element (FIRRE) in DLBCL and its regulation on BCR. Functional impacts of FIRRE on cell viability, transformation, and apoptosis were examined by MTT, colony formation, and flow cytometry, respectively. The interaction between FIRRE and polypyrimidine tract binding protein 1 (PTBP1) was identified by RNA pull‐down and verified using RNA immunoprecipitation (RIP) assays. The effects of FIRRE and PTBP1 on Smurf2 mRNA were examined by RIP, RNA pull‐down, and mRNA stability assays. Smurf2‐mediated BCR ubiquitination was investigated using co‐immunoprecipitation, ubiquitination, and protein stability assays. In vivo, xenograft models were used to assess the impacts of targeting FIRRE on DLBCL growth. FIRRE was specifically up‐regulated in and essentially maintained multiple malignant behaviors of BCR‐dependent DLBCL cells. Through the interaction with PTBP1, FIRRE promoted the mRNA decay of Smurf2, a ubiquitin ligase for the degradation BCR protein. Targeting FIRRE was sufficient to regulat Smurf2 and BCR expressions and inhibit DLBCL malignancy both in vivo and in vitro. FIRRE‐PTBP1 interaction, by simulating Smurf2 mRNA decay and stabilizing BCR, promotes the development of DLBCL. Consequently, targeting this signaling mechanism may provide therapeutic benefits for DLBCL.</jats:p>","journal":"Hematological Oncology","year":2022,"id":632041,"datarank":0.5257802752958799,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.1530442778276798,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.1530442778276798,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":11,"citers_with_citation_signal":9,"citers_with_endowment":9,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1638194,"name":"Guan‐Rong Dai","orcid":null,"position":1,"is_corresponding":false},{"id":546868,"name":"Yi Wu","orcid":"0000-0002-6969-4552","position":2,"is_corresponding":false},{"id":1638195,"name":"Xiao‐Nan Wang","orcid":null,"position":3,"is_corresponding":false},{"id":1638196,"name":"Ming‐Yue Song","orcid":null,"position":4,"is_corresponding":false},{"id":1638197,"name":"Xiao‐Dan Li","orcid":null,"position":5,"is_corresponding":false},{"id":1638198,"name":"Zhengsheng Wu","orcid":null,"position":6,"is_corresponding":false},{"id":1638199,"name":"Rui‐Xiang Xia","orcid":"0000-0003-2222-3216","position":7,"is_corresponding":false},{"id":1638192,"name":"Qin‐Hua Liu","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"LncRNA FIRRE stimulates PTBP1‐induced Smurf2 decay, stabilizes B‐cell receptor, and promotes the development of diffuse large B‐cell lymphoma","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Sustained expression of B‐cell receptor (BCR) critically contributes to the development of diffuse large B‐cell lymphoma (DLBCL). However, little is known on the mechanism regulating BCR expression. In the present study, we explored the biological significance of functional intergenic repeating RNA element (FIRRE) in DLBCL and its regulation on BCR. Functional impacts of FIRRE on cell viability, transformation, and apoptosis were examined by MTT, colony formation, and flow cytometry, respectively. The interaction between FIRRE and polypyrimidine tract binding protein 1 (PTBP1) was identified by RNA pull‐down and verified using RNA immunoprecipitation (RIP) assays. The effects of FIRRE and PTBP1 on Smurf2 mRNA were examined by RIP, RNA pull‐down, and mRNA stability assays. Smurf2‐mediated BCR ubiquitination was investigated using co‐immunoprecipitation, ubiquitination, and protein stability assays. In vivo, xenograft models were used to assess the impacts of targeting FIRRE on DLBCL growth. FIRRE was specifically up‐regulated in and essentially maintained multiple malignant behaviors of BCR‐dependent DLBCL cells. Through the interaction with PTBP1, FIRRE promoted the mRNA decay of Smurf2, a ubiquitin ligase for the degradation BCR protein. Targeting FIRRE was sufficient to regulat Smurf2 and BCR expressions and inhibit DLBCL malignancy both in vivo and in vitro. FIRRE‐PTBP1 interaction, by simulating Smurf2 mRNA decay and stabilizing BCR, promotes the development of DLBCL. Consequently, targeting this signaling mechanism may provide therapeutic benefits for DLBCL.</jats:p>","is_dataset_classified":null,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"35416325","pmcid":null,"openalex_id":"https://openalex.org/W4223573505","authors":[],"funders":[{"funder_name":"the Anhui Medical University 2020 School Research Fund","grant_id":"2020xkj163","title":null},{"funder_name":"Research Fund of Anhui Institute of Translational Medicine","grant_id":"2021zhyx-C39","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82174011","title":null},{"funder_name":"the Anhui Medical University 2020 School Research Fund (2020xkj163)","grant_id":"","title":null},{"funder_name":"Research Fund of Anhui Institute of Translational Medicine (2021zhyx-C39)","grant_id":"","title":null},{"funder_name":"Research Fund of Anhui Institute of Translational Medicine (2021zhyx-C39)","grant_id":"","title":null},{"funder_name":"the Anhui Medical University 2020 School Research Fund (2020xkj163)","grant_id":"","title":null}],"total_grants":7,"fwci":0.925,"citation_percentile":0.70786851,"influential_citations":0,"citation_trend":[{"year":2022,"count":1},{"year":2023,"count":3},{"year":2024,"count":3},{"year":2025,"count":4}],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/hon.3004","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1002/hon.3004","host_type":"publisher"},{"url":"https://doi.org/10.1002/hon.3004","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/35416325","host_type":"repository"}],"fields_of_study":["Cancer-related molecular mechanisms research","Lymphoma Diagnosis and Treatment","RNA Research and Splicing","Cell Line, Tumor","Heterogeneous-Nuclear Ribonucleoproteins","Humans","Ligases","Lymphoma, Large B-Cell, Diffuse","Polypyrimidine Tract-Binding Protein","RNA, Long Noncoding","RNA, Messenger","Receptors, Antigen, B-Cell","Ubiquitin-Protein Ligases"],"mesh_terms":["Humans","Ligases","Receptors, Antigen, B-Cell","RNA, Messenger","Lymphoma, Large B-Cell, Diffuse","Heterogeneous-Nuclear Ribonucleoproteins","Polypyrimidine Tract-Binding Protein","Ubiquitin-Protein Ligases","Cell Line, Tumor","RNA, Long Noncoding"],"keywords":["Cancer research","breakpoint cluster region","Biology","Cell cycle","RNA-binding protein","RNA","Diffuse large B-cell lymphoma","Immunoprecipitation","Ubiquitin ligase","Molecular biology","Cell growth","Messenger RNA","Cell biology","Cell","Ubiquitin","Chemistry","Lymphoma","Cell culture","Receptor","Gene","Immunology","Biochemistry","Genetics","Dlbcl","Smurf2","B-cell Receptor","Ptbp1","Firre"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T01:29:57.630865Z","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":[]}