ER‐Localized Deadenylase PNLDC1 Suppresses Colorectal Cancer Progression by Targeting the mRNA Decay of TUBB4B
8 affiliations
- 1Department of Urology, Children's Hospital, Zhejiang University School of Medicine National Clinical Research Center for Children and Adolescents’ Health and Diseases Hangzhou China
- 2School of Basic Medical Sciences and Forensic Medicine Hangzhou Medical College Hangzhou Zhejiang China
- 3Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital Guangxi Clinical Research Center for Colorectal Cancer Nanning, Guangxi Autonomous Region China
- 4Department of Gastrointestinal Surgery The First Affiliated Hospital of Zhejiang Chinese Medical University Hangzhou China
- 5Department of Big Data in Health Science School of Public Health and The Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang China
- 6Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology School of Life Sciences Shandong University Qingdao China
- 7Institute of Translational Medicine Zhejiang University School of Medicine Hangzhou China
- 8State Key Laboratory of Biomembrane and Membrane Biotechnology School of Life Science Tsinghua University Beijing China
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.
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BibTeX
@article{liu2026erlocalized,
title = {{ER‐Localized Deadenylase PNLDC1 Suppresses Colorectal Cancer Progression by Targeting the mRNA Decay of TUBB4B}},
author = {Lexin Liu and Yuelin Guan and Yuzhou Qin and Guiping Chen and Guozhen Wang and Xiang Yan and Xue Li and Lei Sun and Wei Yu and Shi Ouyang and Zhichao Ma and Zihao Xu and Zhongkai Cao and Fan Yu and Tong Zhou and Ziyou Luo and Xiangjun Chen and Yongbin Yan and Lidan Hu},
journal = {Exploration},
year = {2026},
month = sep,
doi = {10.1002/exp2.70222},
url = {https://doi.org/10.1002/exp2.70222},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - ER‐Localized Deadenylase PNLDC1 Suppresses Colorectal Cancer Progression by Targeting the mRNA Decay of TUBB4B
AU - Lexin Liu
AU - Yuelin Guan
AU - Yuzhou Qin
AU - Guiping Chen
AU - Guozhen Wang
AU - Xiang Yan
AU - Xue Li
AU - Lei Sun
AU - Wei Yu
AU - Shi Ouyang
AU - Zhichao Ma
AU - Zihao Xu
AU - Zhongkai Cao
AU - Fan Yu
AU - Tong Zhou
AU - Ziyou Luo
AU - Xiangjun Chen
AU - Yongbin Yan
AU - Lidan Hu
PY - 2026
DA - 2026/09/21
JO - Exploration
DO - 10.1002/exp2.70222
UR - https://doi.org/10.1002/exp2.70222
AB - 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.
SN - 2766-8509
SN - 2766-2098
ER -