Yu PJ, Zhu SM, Cai BJ, Ma XM, Qiao WJ, Han JJ, Zhang CW. Zfp36 zinc finger CCCH-type inhibits gastric cancer progression by upregulating lipase G and binding its 3’ untranslated region. World J Gastroenterol 2026; 32(47): 122668 [DOI: 10.3748/wjg.122668]
Corresponding Author of This Article
Cheng-Wu Zhang, Professor, Department of Gastrointestinal Oncology Surgery, Qinghai University Affiliated Hospital (School of Clinical Medicine), No. 29 Tongren Road, Chengdong District, Xining 810001, Qinghai Province, China. 952068360@qq.com
Research Domain of This Article
Biochemistry & Molecular Biology
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research-article
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Yu PJ, Zhu SM, Cai BJ, Ma XM, Qiao WJ, Han JJ, Zhang CW. Zfp36 zinc finger CCCH-type inhibits gastric cancer progression by upregulating lipase G and binding its 3’ untranslated region. World J Gastroenterol 2026; 32(47): 122668 [DOI: 10.3748/wjg.122668]
Peng-Jie Yu, Sheng-Mao Zhu, Bao-Jia Cai, Xiao-Ming Ma, Wen-Jie Qiao, Jing-Jun Han, Cheng-Wu Zhang, Department of Gastrointestinal Oncology Surgery, Qinghai University Affiliated Hospital (School of Clinical Medicine), Xining 810001, Qinghai Province, China
Author contributions: Yu PJ and Zhu SM contributed to conceptualization; Zhu SM, Qiao WJ, and Han JJ contributed to methodology and investigation; Yu PJ contributed to editing, supervision, resources, and project administration; Zhu SM contributed to writing-original draft and data curation; Cai BJ and Ma XM contributed to visualization and validation; Qiao WJ and Han JJ contributed to cell culture, in vitro experiments, in vivo experiments, software, and formal analysis; Zhang CW contributed to guidance, advisor, and decision making as corresponding author. All authors approved the final version to publish.
AI contribution statement: Portions of this manuscript were edited using AI tools solely for language refinement.
Supported by Qinghai Provincial Department of Science and Technology, No. 2023-ZJ-787.
Institutional animal care and use committee statement: The study was approved by the Scientific Research Ethics Committee of The Affiliated Hospital of Qinghai University, No. P-SL-2023186.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: Raw and processed RNA sequencing and improved RNA immunoprecipitation sequencing data can be found in the ArrayExpress database under the following accession numbers: E-MTAB-16188, E-MTAB-16200.
Corresponding author: Cheng-Wu Zhang, Professor, Department of Gastrointestinal Oncology Surgery, Qinghai University Affiliated Hospital (School of Clinical Medicine), No. 29 Tongren Road, Chengdong District, Xining 810001, Qinghai Province, China. 952068360@qq.com
Received: April 27, 2026 Revised: June 26, 2026 Accepted: July 28, 2026 Published online: December 21, 2026 Processing time: 185 Days and 22 Hours
Abstract
BACKGROUND
Zfp36 zinc finger CCCH-type (ZFP36) is a critical RNA-binding protein that plays key roles in cancer progression. However, its specific functions and underlying mechanisms in gastric cancer (GC) remain poorly understood.
AIM
To investigate the functional role and molecular mechanisms of ZFP36 in GC progression.
METHODS
A stable ZFP36-overexpressing human gastric adenocarcinoma AGS cell line was established. Cell proliferation, cell cycle distribution, apoptosis, migration, and invasion were assessed. To identify downstream targets of ZFP36, RNA sequencing (RNA-seq) and improved RNA immunoprecipitation sequencing (iRIP-seq) were performed. Findings were validated using reverse transcription-quantitative polymerase chain reaction and RNA immunoprecipitation-quantitative polymerase chain reaction. Additionally, a xenograft tumor model was utilized to evaluate tumor growth in vivo, and western blot analysis was conducted to examine lipase G (LIPG) expression.
RESULTS
Overexpression of ZFP36 significantly suppressed proliferation, migration, and invasion of AGS cells, triggered G0/G1 cell cycle arrest, and promoted apoptosis. The anti-tumor effect of ZFP36 was further confirmed in xenograft models. RNA-seq analysis identified 729 differentially expressed genes (510 upregulated and 219 downregulated) and 1729 alternative splicing events regulated by ZFP36. iRIP-seq revealed that ZFP36 binds to target genes via specific sequence motifs. Integrated analysis of RNA-seq and iRIP-seq data identified LIPG as a direct target of ZFP36. ZFP36 was found to bind to the 3’ untranslated region of LIPG mRNA and to promote its expression. Consistent with this, elevated LIPG expression was observed in subcutaneous tumors from ZFP36-overexpressing AGS cells in mice.
CONCLUSION
Our study demonstrates that ZFP36 inhibits GC progression by enhancing LIPG expression and binding to its 3’ untranslated region. The ZFP36-LIPG axis represents a promising therapeutic target for GC therapy.
Core Tip: Zfp36 zinc finger CCCH-type (ZFP36), an RNA-binding protein, has an unclear role in gastric cancer. Here, ZFP36 overexpression in AGS cells suppressed proliferation, migration, and invasion, as well as G0/G1-phase arrest and apoptosis induction, while also inhibiting xenograft tumor growth. Integrated RNA sequencing and improved RNA immunoprecipitation sequencing identified lipase G (LIPG) as a direct target, with ZFP36 binding to its 3’ untranslated region to enhance LIPG expression. In vivo, LIPG was upregulated in ZFP36-overexpressing tumors. These findings demonstrate that ZFP36 inhibits gastric cancer progression by upregulating LIPG, revealing a potential therapeutic axis.
