PABPN1 regulates mRNA alternative polyadenylation to inhibit bladder cancer progression

  • Cell Biosci. 2023 Mar 6;13(1):45. doi: 10.1186/s13578-023-00997-6.
Liang Chen  #  1 ,  Wei Dong  #  1 ,  Menghao Zhou  1 ,  Chenlu Yang  2 ,  Ming Xiong  1 ,  Gallina Kazobinka  3 ,  Zhaohui Chen  1 ,  Yifei Xing  4 ,  Teng Hou  5  6
Affiliations
  • 1. Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 2. Department of Gynecology and Obstetrics, Women and Children Hospital of Guangdong Province, Guangzhou, 510080, China.
  • 3. Urology Unit, La Nouvelle Polyclinique Centrale de Bujumbura, Bujumbura, 378, Burundi.
  • 4. Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. [email protected].
  • 5. Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. [email protected].
  • 6. Department of Urology, South China Hospital, Medical School, Shenzhen University, Shenzhen, 518116, China. [email protected].
  • # Contributed equally.
PMID: 36879298 DOI: 10.1186/s13578-023-00997-6
Abstract

Background: About 10-20% of patients with Bladder Cancer (BC) progress to muscle-invasive diseases, of which the underlying key molecular events have yet to be addressed.

Results: Here, we identified poly(A) binding protein nuclear 1 (PABPN1), a general factor of alternative polyadenylation (APA), was downregulated in BC. Overexpression and knockdown of PABPN1 significantly decreased and increased BC aggressiveness, respectively. Mechanistically, we provide evidence that the preference of PABPN1-bound polyadenylation signals (PASs) depends on the relative location between canonical and non-canonical PASs. PABPN1 shapes inputs converging on Wnt signaling, cell cycle, and lipid biosynthesis.

Conclusions: Together, these findings provide insights into how PABPN1-mediated APA regulation contributes to BC progression, and suggest that pharmacological targeting PABPN1 might have therapeutic potential in patients with BC.

Keywords
Alternative polyadenylation; Bladder cancer; Cell cycle; Lipid biosynthesis; PABPN1; Wnt signaling.
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