Published online Sep 15, 2023. doi: 10.4251/wjgo.v15.i9.1531
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.
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.