Evidence map›Paper›PMID 39833825›Full record

ArticleJournal of translational medicine2025

Modulation of DAPK1 expression by its alternative splice variant DAPK1-215 in cancer.

QingShui Wang, ShuYun Weng, WenTing Zhong, YouYu Lin, Yan Yu, YiMin Huang, LiLin Ge, XiuLi Zhang, FangQin Xue, Yehuda G Assaraf and 1 more

Abstract read
In one paragraph

Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

QingShui WangFujian-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.
ShuYun WengXiamen Ocean Vocational College, Xiamen, 361000, China.
WenTing ZhongThe United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, The Liver Center of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fujian Medical University, Fuzhou, 350001, China.
YouYu LinFujian Normal University, Fuzhou, 350001, China.
Yan YuCollaborative Innovation Center for Rehabilitation Technology, the Institute of Rehabilitation Industry, Fujian University of Traditional Chinese Medicine, Fuzhou, 350001, China.
YiMin HuangCollege of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, China.
LiLin GeJiangsu Province Engineering Research Center of Chinese Medicine Health Care, Nanjing, 210000, China.
XiuLi ZhangFujian-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. zhangxl@fjtcm.edu.cn.
FangQin XueDepartment of Gastrointestinal Surgery, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, No. 134 Dongjie, Fuzhou, China. xuefangqingsl@sina.com.
Yehuda G AssarafThe Fred Wyszkowski Cancer Research Laboratory, Faculty of Biology, Technion-Israel Institute of Technology, 3200003, Haifa, Israel. assaraf@technion.ac.il.
Yao LinFujian-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. yaolin@fjtcm.edu.cn.

Funding

Fujian University of Traditional Chinese Medicine X2023022Natural Science Foundation of Fujian Province 2022J01173Science Fund for Distinguished Young Scholars of Fujian Province 82003095Youth Research and Innovation Cultivation Program of Fujian Univeristy of Tradtional Chinese Medicine XQC2023007
6 · The paper itself

Abstract

backgroundDeath-Associated Protein Kinase 1 (DAPK1) family members are calcium/calmodulin-regulated serine/threonine kinases implicated in cell death, normal development, and human diseases. However, the regulation of DAPK1 expression in cancer remains unclear.

methodsWe examined the expression and functional impact of a DAPK1 splice variant, DAPK1-215, in multiple cancer cell lines. DAPK1 and DAPK1-215 expression levels were quantified by qRT-PCR and Western blotting. Cell migration, invasion, and proliferation assays were conducted in vitro, and a zebrafish model was employed to evaluate metastatic potential. RNA pull-down and CLIP-seq analyses were performed to identify potential RNA-binding proteins. Finally, clinical liver cancer specimens were analyzed to assess the prognostic relevance of DAPK1-215 and DAPK1 mRNA levels.

resultsDAPK1-215 downregulated DAPK1 expression in liver, kidney, and gastric cancer cells by reducing DAPK1 mRNA stability. DAPK1-215 promoted migratory and invasive capabilities in liver and kidney cancer cells, but inhibited these processes in gastric cancer cells, without affecting cell proliferation. Mechanistically, DEAD-Box Helicase 3 X-Linked (DDX3X) stabilized both DAPK1-215 and DAPK1 mRNAs, suggesting that DAPK1-215 may act by competing for DDX3X binding to modulate DAPK1 mRNA stability. Importantly, high levels of DAPK1-215 correlated inversely with DAPK1 mRNA in liver cancer specimens and predicted poor prognosis, whereas high DAPK1 expression predicted improved patient outcomes.

conclusionsOur findings unveil DAPK1-215 as a molecular brake on DAPK1 expression, influencing cancer cell migration and invasion in a context-dependent manner. These results highlight the potential of DAPK1-215 as an important regulator of malignant progression and as a prognostic marker in liver cancer.

Indexed as

Alternative SplicingDeath-Associated Protein KinasesGene Expression Regulation, NeoplasticNeoplasmsAnimalsCell Line, TumorCell MovementCell ProliferationDEAD-box RNA HelicasesHumansNeoplasm InvasivenessPrognosisProtein IsoformsRNA, MessengerRNA StabilityZebrafishDAPK1 protein, humanDEAD-box RNA HelicasesDeath-Associated Protein KinasesProtein IsoformsRNA, MessengerCancer progressionDAPK1DAPK1-215DDX3XMRNA stability

Identifiers

PMID39833825
PMCPMC11744996

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.