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Background <p>Colorectal cancer (CRC) is a disease leading cause of death worldwide. Lacking molecular markers for early detection and suitable candidates for targeted therapies are two main reasons for causing CRC malignancy.</p> Objectives <p>Exploring the role of NUDT21 in colorectal cancer metastasis.</p> Methods <p>A systematic bioinformatic analysis identified key genes involved in colorectal cancer, which were subsequently validated through loss-of-function and gain-of-function experiments conducted both in vitro and in vivo.</p> Results <p>Overexpression of nucleoside diphosphate linked moiety X hydrolases-type motif 21 (NUDT21), a critical factor that regulates alternative polyadenylation, is observed in malignant polyps and in human and mouse CRC. Survival analysis reveals that high level of NUDT21 is associated with poor prognosis. NUDT21 knockdown not only inhibits cell growth but also reduces malignancy traits like anchorage-independent growth and cancer stemness. RNA-seq and RIP-seq results show NUDT21 preferentially binds to the proximal alternative polyadenylation site of numerous oncogenes to promote their expression and thus drive the progression of CRC. Treatment with re-purposing drugs targeting NUDT21 exhibit therapeutic potential in cell culture, organoid, orthotopic, and patient-derived xenografted CRC models.</p> Conclusions <p>These findings demonstrate that NUDT21 is a critical regulator of colon cancer progression and a promising therapeutic target for CRC.</p>

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Targeting NUDT21-mediated alternative polyadenylation of oncogenes ameliorates colorectal cancer malignancy and metastasis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月6日

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  • Shih-Chieh Lin,
  • Ya-Chuan Tsai,
  • Jui-Lin Wang,
  • Hsian-Jean Chin,
  • Ching-Chin Tsai,
  • Shin-Chih Lin,
  • Yi-Syuan Lin,
  • Bo-Wen Lin,
  • Shaw-Jenq Tsai

摘要

Background

Colorectal cancer (CRC) is a disease leading cause of death worldwide. Lacking molecular markers for early detection and suitable candidates for targeted therapies are two main reasons for causing CRC malignancy.

Objectives

Exploring the role of NUDT21 in colorectal cancer metastasis.

Methods

A systematic bioinformatic analysis identified key genes involved in colorectal cancer, which were subsequently validated through loss-of-function and gain-of-function experiments conducted both in vitro and in vivo.

Results

Overexpression of nucleoside diphosphate linked moiety X hydrolases-type motif 21 (NUDT21), a critical factor that regulates alternative polyadenylation, is observed in malignant polyps and in human and mouse CRC. Survival analysis reveals that high level of NUDT21 is associated with poor prognosis. NUDT21 knockdown not only inhibits cell growth but also reduces malignancy traits like anchorage-independent growth and cancer stemness. RNA-seq and RIP-seq results show NUDT21 preferentially binds to the proximal alternative polyadenylation site of numerous oncogenes to promote their expression and thus drive the progression of CRC. Treatment with re-purposing drugs targeting NUDT21 exhibit therapeutic potential in cell culture, organoid, orthotopic, and patient-derived xenografted CRC models.

Conclusions

These findings demonstrate that NUDT21 is a critical regulator of colon cancer progression and a promising therapeutic target for CRC.