{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:04:23Z","timestamp":1790049863661,"version":"4.0.1"},"reference-count":83,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32271311"],"award-info":[{"award-number":["32271311"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82200784"],"award-info":[{"award-number":["82200784"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Exploration"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Colorectal cancer (CRC) remains a leading cause of cancer\u2010related mortality, highlighting the urgent need for novel therapeutic strategies. In this study, we find that PARN\u2010like Domain Containing protein\u20101 (PNLDC1), an endoplasmic reticulum\u2010localized deadenylase, lower expresses in 91 clinical CRC tissues. Using both in vitro and in vivo models, we identify PNLDC1 as a key tumor suppressor by modulating cell cycle progression in CRC. RNA\u2010immunoprecipitation and sequencing analyses reveal that PNLDC1 binds cell cycle\u2010associated mRNAs, with\n                    <jats:italic>TUBB4B<\/jats:italic>\n                    emerging as a critical target. PNLDC1 downregulates\n                    <jats:italic>TUBB4B<\/jats:italic>\n                    mRNA, whose regulated degradation is essential for PNLDC1's tumor\u2010suppressive function. Restoration of TUBB4B expression counteracts PNLDC1\u2010mediated suppression of CRC cell proliferation, underscoring its pivotal role in CRC pathogenesis. Importantly, we demonstrate that the TUBB4B inhibitor, mebendazole, effectively suppresses the enhanced proliferation in lower\u2010expression PNLDC1 models, including cell, mouse xenografts, and patient\u2010derived tumor\u2010like cell clusters, positioning it as a promising therapeutic agent. These findings establish PNLDC1 as a valuable biomarker and therapeutic target, paving the way for developing novel CRC treatments.\n                  <\/jats:p>","DOI":"10.1002\/exp2.70222","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T03:39:52Z","timestamp":1790048392000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ER\u2010Localized Deadenylase\n                    <i>PNLDC1<\/i>\n                    Suppresses Colorectal Cancer Progression by Targeting the mRNA Decay of\n                    <i>TUBB4B<\/i>"],"prefix":"10.1002","author":[{"given":"Lexin","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Urology, Children's Hospital, Zhejiang University School of Medicine National Clinical Research Center for Children and Adolescents\u2019 Health and Diseases  Hangzhou China"},{"name":"School of Basic Medical Sciences and Forensic Medicine Hangzhou 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