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Updated: Jul 6, 2025

Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies
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CPSF3 inhibition blocks pancreatic cancer cell proliferation through disruption of core histone mRNA processing

Abdulrahman A Alahmari1,2, Aditi H Chaubey1, Venkata S Jonnakuti3,4,5

  • 1Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, New York 14203, USA.

RNA (New York, N.Y.)
|January 8, 2024
PubMed

Insights

Cleavage and polyadenylation specificity factor 3 (CPSF3) is highly expressed in pancreatic cancer. Inhibiting CPSF3 blocks tumor growth, offering a new therapeutic strategy for pancreatic ductal adenocarcinoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Pancreatic ductal adenocarcinoma (PDAC) presents a significant challenge due to limited treatment options.
  • Identifying novel therapeutic targets is crucial for improving patient outcomes in PDAC.

Purpose of the Study:

  • To investigate the role of cleavage and polyadenylation specificity factor 3 (CPSF3) as a potential therapeutic target in PDAC.
  • To evaluate the efficacy of inhibiting CPSF3 in PDAC models.

Main Methods:

  • Assessed CPSF3 expression in PDAC tissues and correlated it with patient prognosis.
  • Utilized CRISPR-Cas9 mediated CPSF3 knockdown in PDAC cell lines.
  • Administered the small molecule inhibitor JTE-607 to PDAC cells and in vivo models.
  • Analyzed cell proliferation, colony formation, tumor growth, and cell cycle progression.

Main Results:

  • CPSF3 is overexpressed in PDAC and linked to poorer prognosis.
  • CPSF3 knockdown significantly inhibited PDAC cell proliferation and tumor growth.
  • JTE-607 treatment reduced PDAC cell proliferation and colony formation without affecting normal pancreatic cells.
  • JTE-607 induced transcriptional readthrough of histone genes, decreased histone expression, destabilized chromatin, and caused S-phase cell cycle arrest.

Conclusions:

  • CPSF3 is a promising therapeutic target for pancreatic ductal adenocarcinoma.
  • Inhibition of CPSF3 demonstrates anti-tumor effects in PDAC, supporting its clinical potential.
Keywords:
CPSF3JTE-607alternative polyadenylationchromatin stabilityhistone processing

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