CNPY3’s regulation of tumor microenvironment and its impact on colon cancer aggressiveness

Abstract Background Canopy FGF signaling regulator 3 (CNPY3) has been implicated in tumor progression. However, its specific role in colon cancer (CC) remains unclear. This study aims to investigate the function of CNPY3 in CC and its potential as a therapeutic target. Methods A total of 201 CC tiss...

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Main Authors: Xucan Gao, Biaohuan Zhou, Xiudong Feng, Zhouxin Ji, Qiang Li, Huining Liu
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Molecular Medicine
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Online Access:https://doi.org/10.1186/s10020-025-01145-1
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author Xucan Gao
Biaohuan Zhou
Xiudong Feng
Zhouxin Ji
Qiang Li
Huining Liu
author_facet Xucan Gao
Biaohuan Zhou
Xiudong Feng
Zhouxin Ji
Qiang Li
Huining Liu
author_sort Xucan Gao
collection DOAJ
description Abstract Background Canopy FGF signaling regulator 3 (CNPY3) has been implicated in tumor progression. However, its specific role in colon cancer (CC) remains unclear. This study aims to investigate the function of CNPY3 in CC and its potential as a therapeutic target. Methods A total of 201 CC tissue specimens and 67 adjacent non-cancerous tissues were collected for analysis. CNPY3 expression was assessed using immunohistochemistry and quantitative real-time PCR. Functional assays were conducted in CC cell lines (HT-29 and SW-620) following CNPY3 knockdown to evaluate its effects on cell proliferation, migration, and apoptosis. Gene expression profiling, fibroblast co-culture experiments, and in vivo xenograft models were also conducted. Results Increased CNPY3 expression correlated with advanced tumor stages and poorer prognosis. Knockdown of CNPY3 significantly inhibited cell proliferation, migration, and induced apoptosis in CC cell lines. CNPY3 depletion also modulated fibroblast behavior, inhibiting their transformation into cancer-associated fibroblasts. Pathway analysis revealed that CNPY3 knockdown affected the cell cycle and p53 signaling pathways, and reduced activation of the MAPK and PI3K/AKT pathways. Additionally, CNPY3 knockdown enhanced CC cell sensitivity to 5-fluorouracil. In vivo studies demonstrated that CNPY3 knockdown resulted in smaller tumor sizes and weights than controls. Conclusions CNPY3 is a crucial regulator in CC progression, correlating with tumor aggressiveness and poor patient outcomes. Targeting CNPY3 may offer a promising therapeutic strategy and a valuable prognostic marker in CC management.
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spelling doaj-art-8e933d3e1fa6427b96fac61d36ca95072025-08-20T03:05:55ZengBMCMolecular Medicine1528-36582025-03-0131111510.1186/s10020-025-01145-1CNPY3’s regulation of tumor microenvironment and its impact on colon cancer aggressivenessXucan Gao0Biaohuan Zhou1Xiudong Feng2Zhouxin Ji3Qiang Li4Huining Liu5Department of Anorectal Surgery, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology)Department of Anorectal Surgery, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology)Department of Operating Room, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology)Department of Anorectal Surgery, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology)Department of Anorectal Surgery, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology)Department of Anorectal Surgery, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology)Abstract Background Canopy FGF signaling regulator 3 (CNPY3) has been implicated in tumor progression. However, its specific role in colon cancer (CC) remains unclear. This study aims to investigate the function of CNPY3 in CC and its potential as a therapeutic target. Methods A total of 201 CC tissue specimens and 67 adjacent non-cancerous tissues were collected for analysis. CNPY3 expression was assessed using immunohistochemistry and quantitative real-time PCR. Functional assays were conducted in CC cell lines (HT-29 and SW-620) following CNPY3 knockdown to evaluate its effects on cell proliferation, migration, and apoptosis. Gene expression profiling, fibroblast co-culture experiments, and in vivo xenograft models were also conducted. Results Increased CNPY3 expression correlated with advanced tumor stages and poorer prognosis. Knockdown of CNPY3 significantly inhibited cell proliferation, migration, and induced apoptosis in CC cell lines. CNPY3 depletion also modulated fibroblast behavior, inhibiting their transformation into cancer-associated fibroblasts. Pathway analysis revealed that CNPY3 knockdown affected the cell cycle and p53 signaling pathways, and reduced activation of the MAPK and PI3K/AKT pathways. Additionally, CNPY3 knockdown enhanced CC cell sensitivity to 5-fluorouracil. In vivo studies demonstrated that CNPY3 knockdown resulted in smaller tumor sizes and weights than controls. Conclusions CNPY3 is a crucial regulator in CC progression, correlating with tumor aggressiveness and poor patient outcomes. Targeting CNPY3 may offer a promising therapeutic strategy and a valuable prognostic marker in CC management.https://doi.org/10.1186/s10020-025-01145-1CNPY3Colon cancerTumor microenvironmentBiomarkerTumorigenesis
spellingShingle Xucan Gao
Biaohuan Zhou
Xiudong Feng
Zhouxin Ji
Qiang Li
Huining Liu
CNPY3’s regulation of tumor microenvironment and its impact on colon cancer aggressiveness
Molecular Medicine
CNPY3
Colon cancer
Tumor microenvironment
Biomarker
Tumorigenesis
title CNPY3’s regulation of tumor microenvironment and its impact on colon cancer aggressiveness
title_full CNPY3’s regulation of tumor microenvironment and its impact on colon cancer aggressiveness
title_fullStr CNPY3’s regulation of tumor microenvironment and its impact on colon cancer aggressiveness
title_full_unstemmed CNPY3’s regulation of tumor microenvironment and its impact on colon cancer aggressiveness
title_short CNPY3’s regulation of tumor microenvironment and its impact on colon cancer aggressiveness
title_sort cnpy3 s regulation of tumor microenvironment and its impact on colon cancer aggressiveness
topic CNPY3
Colon cancer
Tumor microenvironment
Biomarker
Tumorigenesis
url https://doi.org/10.1186/s10020-025-01145-1
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