Amylin inhibits gastric cancer progression by targeting CCN1 and affecting the PI3K/AKT signalling pathway

Background: After glucagon and insulin, amylin is the third most significant and active islet hormone. Amylin and insulin act synergistically to suppress postprandial blood glucose levels. Research has shown that insulin plays a vital role in the growth and progression of cancer; however, the relati...

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Main Authors: Li Liu, Wenxuan Liu, Wenhong Deng
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Annals of Medicine
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Online Access:https://www.tandfonline.com/doi/10.1080/07853890.2025.2480754
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author Li Liu
Wenxuan Liu
Wenhong Deng
author_facet Li Liu
Wenxuan Liu
Wenhong Deng
author_sort Li Liu
collection DOAJ
description Background: After glucagon and insulin, amylin is the third most significant and active islet hormone. Amylin and insulin act synergistically to suppress postprandial blood glucose levels. Research has shown that insulin plays a vital role in the growth and progression of cancer; however, the relationship between amylin and gastric cancer (GC) is unclear.Methods This study used a combination of in vitro and in vivo experiments to investigate the role of amylin in the progression of GC. The expression of amylin in GC and its clinical correlation were evaluated using 38 pairs of GC and healthy human clinical samples. In vitro studies, human GC cell lines were treated with amylin to evaluate the effects of amylin on the proliferation, apoptosis and migration of GC cells. In in vivo studies, xenograft mouse models were established by subcutaneous injection of GC cells into nude mice, followed by treatment with amylin to assess tumor growth. Finally, Next-Generation Sequencing Technology (RNA-seq) was used to explore the potential mechanism of amylin on GC.Results We found that amylin expression was reduced in GC compared to adjacent normal gastric tissues and that elevated amylin expression was negatively correlated with adverse pathological factors (p < 0.05). Additionally, we demonstrated that amylin impeded the growth, invasion, migration, and colony formation of GC cells and suppressed the epithelial-to-mesenchymal transformation of these cells (p < 0.05). Tumour xenograft model experiments confirmed the tumour-suppressive effect of amylin in subcutaneous tumours in nude mice (p < 0.05). Transcriptome sequencing (RNA-seq) revealed that amylin significantly down-regulated CCN1 gene expression in GC cells (p < 0.001). Further intervention targeting CCN1 verified its significance as a target of amylin’s anti-carcinogenic function in GC. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that amylin exerted its oncogenic effects by inhibiting the PI3K/Akt signalling pathway (p < 0.05).Conclusions Our findings demonstrate that amylin plays a crucial role in suppressing gastric cancer progression by targeting CCN1 and inhibiting the PI3K/Akt signalling pathway. These results suggest that amylin could serve as a potential therapeutic agent for GC treatment.
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spelling doaj-art-995cab914ed342df96d18da37f3efe6f2025-08-20T01:50:37ZengTaylor & Francis GroupAnnals of Medicine0785-38901365-20602025-12-0157110.1080/07853890.2025.2480754Amylin inhibits gastric cancer progression by targeting CCN1 and affecting the PI3K/AKT signalling pathwayLi Liu0Wenxuan Liu1Wenhong Deng2Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, ChinaDepartment of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, ChinaDepartment of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, ChinaBackground: After glucagon and insulin, amylin is the third most significant and active islet hormone. Amylin and insulin act synergistically to suppress postprandial blood glucose levels. Research has shown that insulin plays a vital role in the growth and progression of cancer; however, the relationship between amylin and gastric cancer (GC) is unclear.Methods This study used a combination of in vitro and in vivo experiments to investigate the role of amylin in the progression of GC. The expression of amylin in GC and its clinical correlation were evaluated using 38 pairs of GC and healthy human clinical samples. In vitro studies, human GC cell lines were treated with amylin to evaluate the effects of amylin on the proliferation, apoptosis and migration of GC cells. In in vivo studies, xenograft mouse models were established by subcutaneous injection of GC cells into nude mice, followed by treatment with amylin to assess tumor growth. Finally, Next-Generation Sequencing Technology (RNA-seq) was used to explore the potential mechanism of amylin on GC.Results We found that amylin expression was reduced in GC compared to adjacent normal gastric tissues and that elevated amylin expression was negatively correlated with adverse pathological factors (p < 0.05). Additionally, we demonstrated that amylin impeded the growth, invasion, migration, and colony formation of GC cells and suppressed the epithelial-to-mesenchymal transformation of these cells (p < 0.05). Tumour xenograft model experiments confirmed the tumour-suppressive effect of amylin in subcutaneous tumours in nude mice (p < 0.05). Transcriptome sequencing (RNA-seq) revealed that amylin significantly down-regulated CCN1 gene expression in GC cells (p < 0.001). Further intervention targeting CCN1 verified its significance as a target of amylin’s anti-carcinogenic function in GC. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that amylin exerted its oncogenic effects by inhibiting the PI3K/Akt signalling pathway (p < 0.05).Conclusions Our findings demonstrate that amylin plays a crucial role in suppressing gastric cancer progression by targeting CCN1 and inhibiting the PI3K/Akt signalling pathway. These results suggest that amylin could serve as a potential therapeutic agent for GC treatment.https://www.tandfonline.com/doi/10.1080/07853890.2025.2480754Amylingastric cancerCCN1transcriptome sequencingEMT
spellingShingle Li Liu
Wenxuan Liu
Wenhong Deng
Amylin inhibits gastric cancer progression by targeting CCN1 and affecting the PI3K/AKT signalling pathway
Annals of Medicine
Amylin
gastric cancer
CCN1
transcriptome sequencing
EMT
title Amylin inhibits gastric cancer progression by targeting CCN1 and affecting the PI3K/AKT signalling pathway
title_full Amylin inhibits gastric cancer progression by targeting CCN1 and affecting the PI3K/AKT signalling pathway
title_fullStr Amylin inhibits gastric cancer progression by targeting CCN1 and affecting the PI3K/AKT signalling pathway
title_full_unstemmed Amylin inhibits gastric cancer progression by targeting CCN1 and affecting the PI3K/AKT signalling pathway
title_short Amylin inhibits gastric cancer progression by targeting CCN1 and affecting the PI3K/AKT signalling pathway
title_sort amylin inhibits gastric cancer progression by targeting ccn1 and affecting the pi3k akt signalling pathway
topic Amylin
gastric cancer
CCN1
transcriptome sequencing
EMT
url https://www.tandfonline.com/doi/10.1080/07853890.2025.2480754
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AT wenxuanliu amylininhibitsgastriccancerprogressionbytargetingccn1andaffectingthepi3kaktsignallingpathway
AT wenhongdeng amylininhibitsgastriccancerprogressionbytargetingccn1andaffectingthepi3kaktsignallingpathway