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

IF 6 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Medicine Pub Date : 2025-03-07 DOI:10.1186/s10020-025-01145-1

Xucan Gao, Biaohuan Zhou, Xiudong Feng, Zhouxin Ji, Qiang Li, Huining Liu

{"title":"CNPY3's regulation of tumor microenvironment and its impact on colon cancer aggressiveness.","authors":"Xucan Gao, Biaohuan Zhou, Xiudong Feng, Zhouxin Ji, Qiang Li, Huining Liu","doi":"10.1186/s10020-025-01145-1","DOIUrl":null,"url":null,"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.","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"89"},"PeriodicalIF":6.0000,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11887163/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s10020-025-01145-1","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

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.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Molecular Medicine 医学-生化与分子生物学

CiteScore

8.60

自引率

0.00%

发文量

137

审稿时长

1 months

期刊介绍： Molecular Medicine is an open access journal that focuses on publishing recent findings related to disease pathogenesis at the molecular or physiological level. These insights can potentially contribute to the development of specific tools for disease diagnosis, treatment, or prevention. The journal considers manuscripts that present material pertinent to the genetic, molecular, or cellular underpinnings of critical physiological or disease processes. Submissions to Molecular Medicine are expected to elucidate the broader implications of the research findings for human disease and medicine in a manner that is accessible to a wide audience.