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

IF 6.4 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

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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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CNPY3对肿瘤微环境的调控及其对结肠癌侵袭性的影响

背景：冠层FGF信号调节因子3 （CNPY3）与肿瘤进展有关。然而，其在结肠癌（CC）中的具体作用尚不清楚。本研究旨在探讨CNPY3在CC中的功能及其作为治疗靶点的潜力。方法：收集201例CC组织标本和67例癌旁非癌组织标本进行分析。采用免疫组织化学和实时荧光定量PCR检测CNPY3的表达。在CC细胞系（HT-29和SW-620）中进行了CNPY3基因敲除后的功能分析，以评估其对细胞增殖、迁移和凋亡的影响。基因表达谱、成纤维细胞共培养实验和体内异种移植物模型也进行了研究。结果：CNPY3表达升高与肿瘤分期晚期、预后较差相关。敲低CNPY3可显著抑制CC细胞系细胞增殖、迁移并诱导细胞凋亡。CNPY3缺失也可以调节成纤维细胞的行为，抑制它们向癌症相关成纤维细胞的转化。通路分析显示，CNPY3敲低影响细胞周期和p53信号通路，降低MAPK和PI3K/AKT通路的激活。此外，CNPY3敲除增强了CC细胞对5-氟尿嘧啶的敏感性。体内研究表明，与对照组相比，CNPY3敲低导致肿瘤大小和重量更小。结论：CNPY3是CC进展的关键调节因子，与肿瘤侵袭性和不良患者预后相关。靶向CNPY3可能提供一种有前途的治疗策略和有价值的CC治疗预后指标。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.