BACKGROUND Colon adenocarcinoma(COAD)is a malignant tumor of the digestive system.The mechanisms underlying COAD development and progression are still largely unknown.AIM To identify the role of canopy FGF signaling r...BACKGROUND Colon adenocarcinoma(COAD)is a malignant tumor of the digestive system.The mechanisms underlying COAD development and progression are still largely unknown.AIM To identify the role of canopy FGF signaling regulator 3(CNPY3)in the development and progression of COAD by using bioinformatic tools and functional experiments.METHODS Bioinformatic data were downloaded from public databases.The associations of clinicopathological features,survival,and immune function with the expression of CNPY3 were analyzed.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses and Gene Set Enrichment Analysis were used to explore the related pathways.Then,quantitative real-time PCR and immunohistochemistry were used for validation of CNPY3 expression in clinical samples and tumor cell lines.Cell lines with CNPY3 knockdown were constructed to further analyze gene functions.The functional experiments included proliferation,invasion,migration and apoptosis assays.RESULTS In both the TCGA cohort and the merged dataset,elevated CNPY3 expression was observed in tumor tissues.High CNPY3 expression correlated with adverse survival and compromised immune functions.Functional enrichment analysis suggested that the pro-oncogenic properties of CNPY3 might be linked to the PI3K-AKT signaling pathway.CNPY3 expression was validated at both the RNA and protein levels.Functional assays indicated that cell proliferation,invasion,and migration were inhibited and cell apoptosis was promoted after CNPY3 knockdown.Additionally,Western blot results revealed the downregulation of key proteins in the PI3K/AKT pathway following CNPY3 knockdown.PI3K/AKT pathway activator reversed the decrease in proliferation,invasion,and migration and the increase in apoptosis.Notably,CNPY3 knockdown still affected the cells when the pathway was inhibited.CONCLUSION This study showed that CNPY3 is upregulated in COAD and might regulate COAD development and progression by the PI3K/AKT pathway.Thus,CNPY3 might be a promising therapeutic target.展开更多
旨在研究成纤维细胞生长因子(FGF20)及受体FGFR2和FGFR3在小鼠胚胎期毛囊形成期的表达情况,了解FGF20及受体FGFR2和FG-FR3在小鼠毛囊形成期的作用。采用实时荧光定量PCR、Western blot和免疫组织化学技术检测胚胎期13 d (E13)至18 d (E...旨在研究成纤维细胞生长因子(FGF20)及受体FGFR2和FGFR3在小鼠胚胎期毛囊形成期的表达情况,了解FGF20及受体FGFR2和FG-FR3在小鼠毛囊形成期的作用。采用实时荧光定量PCR、Western blot和免疫组织化学技术检测胚胎期13 d (E13)至18 d (E18)小鼠背部皮肤中FGF20、FGFR2和FGFR3 mRNA及蛋白的差异表达。免疫组化结果显示,FGF20蛋白和FGFR3蛋白E13在表层细胞微弱表达,E14主要表达在表层细胞,且在基底层细胞也有微弱表达,E15主要表达在基板和表层细胞,E16强表达在毛钉与表层细胞,E17和E18主要表达在表层细胞和未成熟的毛囊;FGFR2蛋白在表层细胞、基底层细胞、基板、毛钉、未成熟的毛囊等处均有表达,且E18强表达在表层细胞和未成熟毛囊;RT-PCR及Western blot数据分析结果显示:FGF20 mRNA及蛋白在E16相对表达量最高;FGFR2 mRNA及蛋白在E13相对表达量最低,E18相对表达量最高;FGFR3 mRNA及蛋白表达趋势和FGF20相似。研究结果提示,在毛囊形成期,FGF20可能通过与FGFR3结合从而参与毛囊的诱导和激活,促进毛囊形成并决定其生长方向。FGFR2可能在毛囊形成过程调控表层细胞增殖,促进毛囊形成,诱导毛囊进入第一生长周期。展开更多
文摘BACKGROUND Colon adenocarcinoma(COAD)is a malignant tumor of the digestive system.The mechanisms underlying COAD development and progression are still largely unknown.AIM To identify the role of canopy FGF signaling regulator 3(CNPY3)in the development and progression of COAD by using bioinformatic tools and functional experiments.METHODS Bioinformatic data were downloaded from public databases.The associations of clinicopathological features,survival,and immune function with the expression of CNPY3 were analyzed.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses and Gene Set Enrichment Analysis were used to explore the related pathways.Then,quantitative real-time PCR and immunohistochemistry were used for validation of CNPY3 expression in clinical samples and tumor cell lines.Cell lines with CNPY3 knockdown were constructed to further analyze gene functions.The functional experiments included proliferation,invasion,migration and apoptosis assays.RESULTS In both the TCGA cohort and the merged dataset,elevated CNPY3 expression was observed in tumor tissues.High CNPY3 expression correlated with adverse survival and compromised immune functions.Functional enrichment analysis suggested that the pro-oncogenic properties of CNPY3 might be linked to the PI3K-AKT signaling pathway.CNPY3 expression was validated at both the RNA and protein levels.Functional assays indicated that cell proliferation,invasion,and migration were inhibited and cell apoptosis was promoted after CNPY3 knockdown.Additionally,Western blot results revealed the downregulation of key proteins in the PI3K/AKT pathway following CNPY3 knockdown.PI3K/AKT pathway activator reversed the decrease in proliferation,invasion,and migration and the increase in apoptosis.Notably,CNPY3 knockdown still affected the cells when the pathway was inhibited.CONCLUSION This study showed that CNPY3 is upregulated in COAD and might regulate COAD development and progression by the PI3K/AKT pathway.Thus,CNPY3 might be a promising therapeutic target.
