{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:21:28Z","timestamp":1753878088633,"version":"3.41.2"},"reference-count":35,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Thoracic Cancer"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Chemotherapy is crucial for treating pleural mesothelioma; however, the outcomes are poor, necessitating an urgent need to study the mechanism of chemotherapy resistance in mesothelioma cells. Human antigen R (HuR), an RNA\u2010binding protein and key post\u2010transcriptional regulator of mRNA, is linked to poor prognosis in cancers like mesothelioma. We investigated the involvement of cytoplasmic HuR expression in drug resistance mechanisms in mesothelioma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrospectively evaluated cytoplasmic HuR expression in 30 patients with pleural mesothelioma who underwent surgical resection using immunohistochemistry. We also examined the role of forced cytoplasmic expression of HuR in drug resistance using mesothelioma cell lines and performed RNA\u2010Seq analysis to identify gene expression changes responsible for drug resistance acquisition via HuR cytoplasmic expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients with mesotheliomas who expressed cytoplasmic HuR exhibited significantly worse disease\u2010free survival following post\u2010operative chemotherapy. Forced cytoplasmic HuR expression in mesothelioma cell lines increased chemotherapy resistance through increased expression of <jats:italic>CALB2<\/jats:italic>, upregulation of the E2F pathway and suppression of the p53 pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Cytoplasmic HuR expression increases the chemoresistance and postoperative recurrence risk of pleural mesothelioma, making it a potential biomarker for predicting therapeutic prognosis. However, the mechanism of HuR transfer to the cytoplasm remains unclear for therapeutic application.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1759-7714.70062","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T07:25:14Z","timestamp":1744183514000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cytoplasmic <scp>HuR<\/scp> Expression Enhances Chemoresistance in Pleural Mesothelioma Through Increased Expression of <scp>CALB2<\/scp>, Promotion of the <scp>E2F<\/scp> Pathway, and Suppression of the p53 Pathway"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8449-2068","authenticated-orcid":false,"given":"Susumu","family":"Kirimura","sequence":"first","affiliation":[{"name":"Division of Pathology Institute of Science Tokyo Hospital  Tokyo 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