{"doi":"10.1093/carcin/bgaf039","title":"BRINP3 promotes lung adenocarcinoma by enhancing CLOCK-mediated transcriptional regulation of CRYZL1 and activating the AKT pathway","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Lung cancer, particularly lung adenocarcinoma (LUAD), is the leading cause of cancer-related death globally. This study investigated the role of BRINP3 in LUAD. Immunohistochemical analysis revealed significantly upregulated BRINP3 expression in LUAD tissues compared to normal tissues, mainly located in the cytoplasm and positively correlated with tumor progression. RNA sequencing data from the TCGA-LUAD database corroborated these findings. Elevated BRINP3 expression was associated with advanced tumor stages, higher malignancy grades, and increased risk of lymphatic metastasis. Functional studies showed that BRINP3 knockdown inhibited cell proliferation, colony formation, and migration, while promoting apoptosis. Conversely, BRINP3 overexpression enhanced these malignant behaviors. Gene expression profiling identified CLOCK and CRYZL1 as potential BRINP3 targets, with BRINP3 interacting with CLOCK to regulate CRYZL1 transcription. Additionally, BRINP3 activated the AKT signaling pathway to promote LUAD progression. In vivo experiments validated the tumor-suppressing effects of BRINP3 knockdown, reducing tumor growth and metastatic potential. In conclusion, BRINP3 played a crucial role in LUAD development and progression by regulating CLOCK-mediated transcriptional regulation of CRYZL1 and activating the AKT signaling pathway. BRINP3 knockdown inhibited LUAD cell malignancy and might represent a potential therapeutic target.</jats:p>","journal":"Carcinogenesis","year":2025,"id":596539,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":1311346,"name":"Cheng Huang","orcid":"0000-0002-7149-9879","position":1,"is_corresponding":false},{"id":1527832,"name":"Yeye Chen","orcid":"0000-0001-6654-7701","position":2,"is_corresponding":false},{"id":556378,"name":"Lei Liu","orcid":"0000-0001-7782-4559","position":3,"is_corresponding":false},{"id":1527834,"name":"Shanqing Li","orcid":"0000-0003-2437-1108","position":4,"is_corresponding":false},{"id":249698,"name":"Ye Zhang","orcid":"0000-0002-2573-5471","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"BRINP3 promotes lung adenocarcinoma by enhancing CLOCK-mediated transcriptional regulation of CRYZL1 and activating the AKT pathway","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Lung cancer, particularly lung adenocarcinoma (LUAD), is the leading cause of cancer-related death globally. This study investigated the role of BRINP3 in LUAD. Immunohistochemical analysis revealed significantly upregulated BRINP3 expression in LUAD tissues compared to normal tissues, mainly located in the cytoplasm and positively correlated with tumor progression. RNA sequencing data from the TCGA-LUAD database corroborated these findings. Elevated BRINP3 expression was associated with advanced tumor stages, higher malignancy grades, and increased risk of lymphatic metastasis. Functional studies showed that BRINP3 knockdown inhibited cell proliferation, colony formation, and migration, while promoting apoptosis. Conversely, BRINP3 overexpression enhanced these malignant behaviors. Gene expression profiling identified CLOCK and CRYZL1 as potential BRINP3 targets, with BRINP3 interacting with CLOCK to regulate CRYZL1 transcription. Additionally, BRINP3 activated the AKT signaling pathway to promote LUAD progression. In vivo experiments validated the tumor-suppressing effects of BRINP3 knockdown, reducing tumor growth and metastatic potential. In conclusion, BRINP3 played a crucial role in LUAD development and progression by regulating CLOCK-mediated transcriptional regulation of CRYZL1 and activating the AKT signaling pathway. BRINP3 knockdown inhibited LUAD cell malignancy and might represent a potential therapeutic target.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40799124","pmcid":null,"openalex_id":null,"authors":[],"funders":[{"funder_name":"National High Level Hospital Clinical Research Funding","grant_id":"2022-PUMCH-B-012","title":null}],"total_grants":1,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"closed","license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://academic.oup.com/carcin/advance-article-pdf/doi/10.1093/carcin/bgaf039/64031698/bgaf039.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/carcin/article-pdf/46/4/bgaf039/64031698/bgaf039.pdf","host_type":"publisher"}],"fields_of_study":[],"mesh_terms":["Animals","Mice, Inbred BALB C","Humans","Mice","Lung Neoplasms","zeta-Crystallins","DNA-Binding Proteins","Xenograft Model Antitumor Assays","Transcription, Genetic","Gene Expression Regulation, Neoplastic","Middle Aged","Female","Male","Proto-Oncogene Proteins c-akt","Metabolic Networks and Pathways","CLOCK Proteins","A549 Cells","Adenocarcinoma of Lung"],"keywords":["Transcriptional regulation","Akt Pathway","Luad","Brinp3","Cryzl1"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-28T10:36:10.830543Z","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":[]}