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Updated: Jun 1, 2025

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
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Modulation of DAPK1 expression by its alternative splice variant DAPK1-215 in cancer

QingShui Wang1, ShuYun Weng2, WenTing Zhong3

  • 1Fujian-Macao Science and Technology Cooperation Base of Traditional Chinese Medicine-Oriented Chronic Disease Prevention and Treatment, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350001, China. wangqingshui@fjnu.edu.cn.

Journal of Translational Medicine
|January 20, 2025
PubMed
Abstract

Insights

A novel splice variant, DAPK1-215, acts as a molecular brake on Death-Associated Protein Kinase 1 (DAPK1) expression, impacting cancer cell migration and invasion. DAPK1-215 serves as a prognostic marker for liver cancer.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Death-Associated Protein Kinase 1 (DAPK1) is a serine/threonine kinase involved in cell death, development, and disease.
  • The regulation of DAPK1 expression in cancer is not well understood.

Purpose of the Study:

  • To investigate the expression and functional role of the DAPK1 splice variant, DAPK1-215, in various cancer types.
  • To elucidate the mechanism by which DAPK1-215 affects DAPK1 expression and cancer cell behavior.
  • To assess the prognostic significance of DAPK1-215 and DAPK1 in liver cancer.

Main Methods:

  • Quantified DAPK1 and DAPK1-215 expression using qRT-PCR and Western blotting in cancer cell lines.
  • Assessed cell migration, invasion, and proliferation in vitro and metastatic potential in a zebrafish model.
  • Utilized RNA pull-down and CLIP-seq to identify RNA-binding proteins.
  • Analyzed clinical liver cancer specimens for prognostic relevance.

Main Results:

  • DAPK1-215 downregulated DAPK1 expression by reducing mRNA stability in liver, kidney, and gastric cancer cells.
  • DAPK1-215 promoted migration and invasion in liver and kidney cancer but inhibited these in gastric cancer cells.
  • DEAD-Box Helicase 3 X-Linked (DDX3X) stabilized both DAPK1 and DAPK1-215 mRNAs, suggesting competition for binding.
  • High DAPK1-215 levels correlated with poor prognosis in liver cancer, while high DAPK1 predicted better outcomes.

Conclusions:

  • DAPK1-215 functions as a molecular brake on DAPK1 expression, influencing cancer cell migration and invasion in a context-dependent manner.
  • DAPK1-215 is a significant regulator of malignant progression and a potential prognostic marker in liver cancer.
Keywords:
DAPK1-215Cancer progressionDAPK1DDX3XMRNA stability

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