ASAP3 disrupts ASAP1-ARHGAP12 to inhibit RhoA and yes-associated protein/transcriptional coactivator with PDZ-binding motif, suppressing gastric cancer progression

doi:10.4251/wjgo.v18.i8.117876

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World Journal of Gastrointestinal Oncology

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1948-5204

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastrointest Oncol. Aug 15, 2026; 18(8): 117876
Published online Aug 15, 2026. doi: 10.4251/wjgo.v18.i8.117876

ASAP3 disrupts ASAP1-ARHGAP12 to inhibit RhoA and yes-associated protein/transcriptional coactivator with PDZ-binding motif, suppressing gastric cancer progression

Xian-Bin Huang, Yuan Deng, Shi-Yi Gong, Miao Yu, Hui Cai

Xian-Bin Huang, Hui Cai, The First Clinical Medical College of Lanzhou University, Lanzhou 730000, Gansu Province, China

Xian-Bin Huang, Yuan Deng, Shi-Yi Gong, Miao Yu, Hui Cai, General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China

Hui Cai, Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China

Hui Cai, NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China

Author contributions: Huang XB, Deng Y, Gong SY, Yu M and Cai H contributed to the study conception and design; Huang XB contributed to conceptualization, methodology, investigation, formal analysis, data curation, writing original draft; Deng Y contributed to methodology, validation, investigation, resources, writing review and editing; Gong SY contributed to software, formal analysis, visualization, writing review and editing; Yu M contributed to resources, supervision, project administration, funding acquisition; Cai H contributed to conceptualization, supervision, writing review and editing, and acted as the corresponding author responsible for all communications and submissions; Huang XB, Deng Y and Gong SY contributed to material preparation, data collection and analysis; The first draft of the manuscript was written by Huang XB, and all authors commented on previous versions of the manuscript; all authors have read and approved the final manuscript.

AI contribution statement: The authors agree to accountability for all content of this manuscript, including any portions for which AI tools were used as assistive technology. The authors confirm that all AI-assisted outputs have been carefully reviewed, verified, and validated. The authors take full responsibility for the accuracy, integrity, and originality of the manuscript. AI tools were not used to generate data, perform analyses, or draw scientific conclusions.

Institutional review board statement: For bioinformatics analysis, ethical compliance was ensured as TCGA data are publicly available and de-identified, requiring no additional institutional review board approval and adhering to TCGA publication guidelines.

Institutional animal care and use committee statement: All animal studies were performed in line with the Animal Research: Reporting in vivo Experiments guidelines 2.0, and were approved by the Institutional Animal Care and Use Committee at Obio Technology (Shanghai) Corp., Ltd. (approval No. OBIO-AUF-182).

Conflict-of-interest statement: The authors declare that they have no conflict of interest.

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: All data supporting the findings of this study are publicly available. All sequencing data generated have been deposited in the National Center for Biotechnology Information databases under the following permanent accession links: BioProject: Accession: PRJNA1381551; Direct URL: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1381551; This page provides an overview of the project and links to all related data. Sequence Read Archive: Project Accession: PRJNA1381551 (linked to the BioProject above); Run Accessions: SRR36466707, SRR36466710, SRR36466704, SRR36466698, SRR36466692, SRR36466706, SRR36466697, SRR36466694, SRR36466711, SRR36466708, SRR36466705, SRR36466701, SRR36466695, SRR36466709, SRR36466703, SRR36466700, SRR36466702, SRR36466699, SRR36466696, SRR36466693. Direct URL to SRA project: https://www.ncbi.nlm.nih.gov/biosample/?term = SAMN54109913. These Run accessions point directly to the raw sequence read files, which reviewers can download for analysis. The data are publicly accessible immediately via the links provided above. The data that support the findings of this study are available from the corresponding author upon reasonable request. Some data are not publicly available due to privacy or ethical restrictions but may be obtained from the corresponding author upon reasonable request and with permission from the relevant ethics committee.

Corresponding author: Hui Cai, MD, Professor, The First Clinical Medical College of Lanzhou University, No. 1 Donggang West Road, Chengguan District, Lanzhou 730000, Gansu Province, China caialonteam@163.com

Received: December 18, 2025
Revised: April 12, 2026
Accepted: May 25, 2026
Published online: August 15, 2026
Processing time: 227 Days and 1.4 Hours

Abstract

BACKGROUND

Gastric cancer (GC) has high global mortality, with limited efficacy of advanced therapies due to unclear pathogenesis. While other ASAP family members like ASAP1 are recognized oncoproteins, the role of ASAP3 in GC is poorly understood.

AIM

To investigate the functions and mechanisms of ASAP3 in GC.

METHODS

The biological effects of ASAP3 were assessed in vitro using AGS and HGC-27 GC cell lines with ASAP3 overexpression or knockdown, evaluating proliferation, apoptosis, migration, and invasion. A subcutaneous xenograft model was used for in vivo validation. Underlying mechanisms were explored via transcriptomics, proteomics, and molecular biology techniques including co-immunoprecipitation and RhoA activation pull down.

RESULTS

ASAP3 expression in HGC-27 cells was significantly higher than that in AGS cells. Functional experiments demonstrated that ASAP3 overexpression suppressed GC cell proliferation, migration, invasion, induced S arrest/apoptosis, and inhibited tumor growth, while its knockdown promoted these malignant phenotypes. Then, transcriptomic and proteomic analyses respectively identified 382/714 differentially expressed messenger RNAs and 98/66 differential expressed proteins between short hairpin (sh)-ASAP3-HGC-27/over-expression (oe)-ASAP3-AGS and sh-negative control (NC)-HGC-27/oe-NC-AGS cells, which significantly enriched in Hippo pathway, and GTPase regulation. Real-time quantitative polymerase chain reaction showed ASAP3 silencing in HGC-27 cells upregulated CCN1, AMOTL2 while downregulated CCN2, while ASAP3 overexpression in AGS cells reversed these trends. Western blot further showed ASAP3 silencing reduced the phosphorylation of MST1/MST2, LATS1/LATS2, yes-associated protein (YAP), and transcriptional coactivator with PDZ-binding motif (TAZ), whereas ASAP3 overexpression in AGS cells enhanced their phosphorylation. Finally, ASAP3 overexpression could inhibit RhoA activity and thus suppress YAP/TAZ activation by interfering with the ASAP1-ARHGAP12 interaction.

CONCLUSION

ASAP3 may inhibit GC oncogenesis/progression by disrupting ASAP1-ARHGAP12 to suppress RhoA/YAP/TAZ, serving as a potential GC therapeutic target.

Keywords: Gastric cancer; ASAP3; RhoA activity; ASAP1-ARHGAP12; Yes-associated protein/transcriptional coactivator with PDZ-binding motif

Core Tip: Our study identified ASAP3 as a novel tumor suppressor in gastric cancer (GC) that may suppress RhoA activity by disrupting the ASAP1-ARHGAP12 interaction, thereby activating the Hippo pathway and suppressing yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ)-mediated oncogenesis. These findings clarify the context-dependent function of ASAP3, uncover a new regulatory mechanism of the RhoA/YAP/TAZ axis, and provide a potential prognostic biomarker and therapeutic target for GC. Future studies will focus on validating ASAP3’s prognostic value in clinical cohorts and developing small-molecule modulators of the ASAP3 interfered ASAP1-ARHGAP12 interaction for GC therapy.