Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Sep 15, 2023; 15(9): 1531-1543
Published online Sep 15, 2023. doi: 10.4251/wjgo.v15.i9.1531
RNA-binding protein CPSF6 regulates IBSP to affect pyroptosis in gastric cancer
Xue-Jun Wang, Yong Liu, Bin Ke, Li Zhang, Han Liang
Xue-Jun Wang, Yong Liu, Bin Ke, Li Zhang, Han Liang, Department of Gastric Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin 300060, China
Author contributions: Wang XJ designed and wrote the manuscript; Liu Y, Ke B, Zhang L, and Liang H collected and analyzed the data; and all authors read and approved the final manuscript.
Supported by the National Key R&D Program of China, No. 2016YFC1303202.
Institutional review board statement: The study was approved by the Ethics Committee of Tianjin Medical University Cancer Institute and Hospital (Approval No. E2020216).
Informed consent statement: Written informed consent was obtained from all patients.
Institutional animal care and use committee statement: This work was reviewed and approved by the Animal Care and Use Committee of Beijing Viewsolid Biotechnology Co. LTD (Approval No. VS212601449).
Conflict-of-interest statement: The authors report no conflict of interest for this article.
Data sharing statement: The data that support the findings of this study are available from the corresponding author.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Xue-Jun Wang, MD, Professor, Department of Gastric Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Huanhu Xi Road, Tiyuan Bei, Hexi District, Tianjin 300060, China.
Received: April 7, 2023
Peer-review started: April 7, 2023
First decision: July 19, 2023
Revised: July 31, 2023
Accepted: August 18, 2023
Article in press: August 18, 2023
Published online: September 15, 2023

Extensive evidence has illustrated the promotive role of integrin binding sialoprotein (IBSP) in the progression of multiple cancers. However, little is known about the functions of IBSP in gastric cancer (GC) progression.


To investigate the mechanism underlying the regulatory effects of IBSP in GC progression, and the relationship between IBSP and cleavage and polyadenylation factor 6 (CPSF6) in this process.


The mRNA and protein expression of relevant genes were assessed through real-time quantitative polymerase chain reaction and Western blot, respectively. Cell viability was evaluated by Cell Counting Kit-8 assay. Cell invasion and migration were evaluated by Transwell assay. Pyroptosis was measured by flow cytometry. The binding between CPSF6 and IBSP was confirmed by luciferase reporter and RNA immunoprecipitation (RIP) assays.


IBSP exhibited higher expression in GC tissues and cell lines than in normal tissues and cell lines. IBSP knockdown suppressed cell proliferation, migration, and invasion but facilitated pyroptosis. In the exploration of the regulatory mechanism of IBSP, potential RNA binding proteins for IBSP were screened with catRAPID omics v2.0. The RNA-binding protein CPSF6 was selected due to its higher expression in stomach adenocarcinoma. Luciferase reporter and RIP assays revealed that CPSF6 binds to the 3’-untranslated region of IBSP and regulates its expression. Knockdown of CPSF6 inhibited cell proliferation, migration, and invasion but boosted pyroptosis. Through rescue assays, it was uncovered that the retarded GC progression mediated by CPSF6 knockdown was reversed by IBSP overexpression.


Our study highlighted the vital role of the CPSF6/IBSP axis in GC, suggesting that IBSP might be an effective bio-target for GC treatment.

Keywords: Integrin binding sialoprotein, Cleavage and polyadenylation factor 6, Pyroptosis, Gastric cancer

Core Tip: This study, for the first time, revealed the crucial role of the cleavage and polyadenylation factor 6 (CPSF6)/integrin binding sialoprotein (IBSP) axis in gastric cancer (GC). This discovery might shed light on GC treatment. However, although this study explored this regulatory axis on cell proliferation, metastasis, and pyroptosis in GC, its data regarding the regulatory effects of CPSF6/IBSP on GC progression are limited. In the future, the regulatory effects of the CPSF6/IBSP axis on stemness, autophagy, and inflammation should be investigated through more experiments.