Epigenetic silencing ZSCAN23 promotes pancreatic cancer growth by activating Wnt signaling

Cancer Biol Ther. 2024 Dec 31;25(1):2302924. doi: 10.1080/15384047.2024.2302924. Epub 2024 Jan 16.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the most malignant tumor. Zinc finger and SCAN domain-containing protein 23 (ZSCAN23) is a new member of the SCAN domain family. The expression regulation and biological function remain to be elucidated. In this study, we explored the epigenetic regulation and the function of ZSCAN23 in PDAC. ZSCAN23 was methylated in 60.21% (171/284) of PDAC and its expression was regulated by promoter region methylation. The expression of ZSCAN23 inhibited cell proliferation, colony formation, migration, invasion, and induced apoptosis and G1/S phase arrest. ZSCAN23 suppressed Panc10.05 cell xenograft growth in mice. Mechanistically, ZSCAN23 inhibited Wnt signaling by interacting with myosin heavy chain 9 (MYH9) in pancreatic cancer cells. ZSCAN23 is frequently methylated in PDAC and may serve as a detective marker. ZSCAN23 suppresses PDAC cell growth both in vitro and in vivo.

Keywords: DNA methylation; Wnt signaling pathway; ZSCAN23; pancreatic ductal adenocarcinoma; tumor suppressor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Pancreatic Ductal* / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Epigenesis, Genetic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Pancreatic Neoplasms* / pathology
  • Wnt Signaling Pathway / genetics
  • Zinc Fingers

Grants and funding

This study was supported by grants from the National Key Research and Development Program of China [2018YFA0208902, 2020YFC2002705], National Natural Science Foundation of China [82272632, 81672138], and Beijing Science Foundation of China [7171008].