中国药理学通报2025,Vol.41Issue(1) :116-121.DOI:10.12360/CPB202406093

CYFIP1对结直肠癌细胞HT29增殖和凋亡的影响

Effect of CYFIP1 on proliferation and apoptosis of colorectal cancer cell HT29

余富龙 李亮 强昊 袁慧 王松 程晓虎 江闰犇 杨雅茹 刘志宁
中国药理学通报2025,Vol.41Issue(1) :116-121.DOI:10.12360/CPB202406093

CYFIP1对结直肠癌细胞HT29增殖和凋亡的影响

Effect of CYFIP1 on proliferation and apoptosis of colorectal cancer cell HT29

余富龙 1李亮 1强昊 2袁慧 1王松 1程晓虎 1江闰犇 1杨雅茹 3刘志宁1
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作者信息

  • 1. 安徽医科大学第二附属医院普外科,安徽 合肥 230000
  • 2. 安徽医科大学,安徽 合肥 230032
  • 3. 安徽医科大学第二附属医院药物临床实验研究中心,安徽 合肥 230000
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摘要

目的 分析 CYFIP1(cytoplasmic FMR1-interacting pro-tein-1,CYFIP1)在结直肠癌中的表达水平,并探究敲低CY-FIP1对结直肠癌细胞HT29增殖与凋亡的影响及其可能机制.方法 通过免疫组化实验检测32例结直肠癌组织及对应癌旁组织中CYFIP1的表达水平;通过GEPIA2数据库筛选共表达基因,预测二者相关性及可能结合位点;构建siR-NA-CYFIP1后,分别用CCK-8、细胞凋亡荧光Hoechst 33342/PI双染实验和Western blot分别检测HT29细胞的增殖、凋亡水平以及细胞凋亡相关蛋白表达水平的变化.结果 免疫组化结果显示结直肠癌组织中CYFIP1的表达水平明显高于其对应的癌旁组织(P<0.05);CYFIP1的表达与患者的年龄、性别无关,与TNM分期,淋巴结转移相关(P<0.05);利用GEPIA2、JASPAR数据库和rVista 2.0启动子预测软件在CYFIP1基因上游的3kbps的DNA区域预测了一个保守的TP53结合位点;HT29转染siRNA-CYFIP1后,细胞增殖能力均明显降低(P<0.05);HT29转染siRNA-CYFIP1后细胞凋亡相关蛋白 cleaved caspase-3 水平升高,caspase-3,Bcl-2的表达水平降低(P<0.05),这可能与CYFIP1与TP53相互作用有关.结论 CYFIP1在结直肠癌中高表达,与TNM分期,以及淋巴结转移相关,敲低CYFIP1后可以抑制结直肠癌细胞HT29的增殖、影响相关凋亡蛋白表达.

Abstract

Aim To investigate the expression levels of cytoplasmic FMR1-interacting protein-1(CYFIP1)in colorectal cancer and assess the impact of CYFIP1 interaction on the proliferation and apoptosis of colorec-tal cancer cell HT29,along with its potential mecha-nisms.Methods Immunohistochemistry was em-ployed to assess CYFIP1 expression in 32 colorectal cancer tissues and adjacent tissues.Coexpressed genes were identified using the GEPIA2 website to predict potential correlations and binding sites.Following the construction of a siRNA-CYFIP1,alterations in cell proliferation,apoptosis,and levels of apoptosis-related proteins were evaluated through CCK-8 assay,Hoechst 33342/PI double staining assay,and Western blot a-nalysis,respectively.Results The immunohisto-chemical findings revealed a significantly elevated level of CYFIP1 expression in colorectal cancer tissues com-pared to paracancer tissues(P<0.05).The expres-sion of CYFIP1 did not show any correlation with age and gender,but exhibited associations with TNM stage and lymph node metastasis(P<0.05).A conserved TP53 binding site was predicted in the 3kbps DNA re-gion upstream of the CYFIP1 gene using GEPIA2,JASPAR databases,and rVista 2.0 promoter prediction software.Following transfection of HT29 cells with siRNA-CYFIP1,the clonogenesis and proliferation of cells significantly decreased(P<0.05).Additional-ly,the levels of cleaved caspase-3 were elevated,while the expression levels of caspase-3 and Bcl-2 were reduced after transfection with siRNA-CYFIP1(P<0.05),which might be related to the interaction be-tween CYFIP1 and TP53.Conclusions The upregu-lation of CYFIP1 in colorectal cancer is associated with TNM stage and lymph node metastasis.Upon silen-cing,CYFIP1 demonstrates the ability to suppress pro-liferation in HT29 cells and modulate the expression of apoptotic proteins.

关键词

结直肠癌/CYFIP1/凋亡/增殖/HT29/小分子干扰RNA

Key words

colorectal cancer/CYFIP1/apoptosis/proliferation/HT29/small molecule interfering RNA

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出版年

2025
中国药理学通报
中国药理学会

中国药理学通报

北大核心
影响因子:1.54
ISSN:1001-1978
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