{
  "abstract": "Colorectal cancer (CRC) remains a leading cause of cancer‐related mortality, highlighting the urgent need for novel therapeutic strategies. In this study, we find that PARN‐like Domain Containing protein‐1 (PNLDC1), an endoplasmic reticulum‐localized 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‐immunoprecipitation and sequencing analyses reveal that PNLDC1 binds cell cycle‐associated mRNAs, with TUBB4B emerging as a critical target. PNLDC1 downregulates TUBB4B mRNA, whose regulated degradation is essential for PNLDC1's tumor‐suppressive function. Restoration of TUBB4B expression counteracts PNLDC1‐mediated 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‐expression PNLDC1 models, including cell, mouse xenografts, and patient‐derived tumor‐like 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.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Urology, Children's Hospital, Zhejiang University School of Medicine National Clinical Research Center for Children and Adolescents’ Health and Diseases Hangzhou China",
    "School of Basic Medical Sciences and Forensic Medicine Hangzhou Medical College Hangzhou Zhejiang China",
    "Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital Guangxi Clinical Research Center for Colorectal Cancer Nanning, Guangxi Autonomous Region China",
    "Department of Gastrointestinal Surgery The First Affiliated Hospital of Zhejiang Chinese Medical University Hangzhou China",
    "Department of Big Data in Health Science School of Public Health and The Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang China",
    "Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology School of Life Sciences Shandong University Qingdao China",
    "Institute of Translational Medicine Zhejiang University School of Medicine Hangzhou China",
    "State Key Laboratory of Biomembrane and Membrane Biotechnology School of Life Science Tsinghua University Beijing China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Lexin Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuelin Guan"
    },
    {
      "affs": [
        2
      ],
      "name": "Yuzhou Qin"
    },
    {
      "affs": [
        3
      ],
      "name": "Guiping Chen"
    },
    {
      "affs": [
        1
      ],
      "name": "Guozhen Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiang Yan"
    },
    {
      "affs": [
        4
      ],
      "name": "Xue Li"
    },
    {
      "affs": [
        5
      ],
      "name": "Lei Sun"
    },
    {
      "affs": [
        6
      ],
      "name": "Wei Yu"
    },
    {
      "affs": [
        0
      ],
      "name": "Shi Ouyang"
    },
    {
      "affs": [
        3
      ],
      "name": "Zhichao Ma"
    },
    {
      "affs": [
        0
      ],
      "name": "Zihao Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhongkai Cao"
    },
    {
      "affs": [
        0
      ],
      "name": "Fan Yu"
    },
    {
      "affs": [
        5
      ],
      "name": "Tong Zhou"
    },
    {
      "affs": [
        5
      ],
      "name": "Ziyou Luo"
    },
    {
      "affs": [
        6
      ],
      "name": "Xiangjun Chen"
    },
    {
      "affs": [
        7
      ],
      "name": "Yongbin Yan"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Lidan Hu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ebe17qczgz16h.bib",
  "cited_by": 0,
  "doi": "10.1002/exp2.70222",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13593926/",
  "id": "ebe17qczgz16h",
  "issns": [
    "2766-8509",
    "2766-2098"
  ],
  "landing_url": "https://doi.org/10.1002/exp2.70222",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
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      "openalex",
      "1312|RNA Research and Splicing"
    ]
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  "openalex": "W7213966193",
  "pdf_url": null,
  "pmcid": "PMC13593926",
  "pmid": "42774471",
  "published": "2026-09-21",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/ebe17qczgz16h.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T12:23:35Z",
      "native_id": "PMC13593926",
      "source": "pmc",
      "url": "https://doi.org/10.1002/exp2.70222"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|RNA Research and Splicing",
      "subfield": "molecular-biology"
    }
  ],
  "title": "ER‐Localized Deadenylase PNLDC1 Suppresses Colorectal Cancer Progression by Targeting the mRNA Decay of TUBB4B",
  "title_text": "ER‐Localized Deadenylase PNLDC1 Suppresses Colorectal Cancer Progression by Targeting the mRNA Decay of TUBB4B",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T12:21:15Z",
  "url": "https://research.draconitic.com/paper/ebe17qczgz16h",
  "venue": "Exploration",
  "versions": []
}