|本期目录/Table of Contents|

[1]王幸如,李晓萌,冯善宇.HOIL-1蛋白切割异常促进小鼠结肠炎相关结直肠癌的发生[J].天津医科大学学报,2026,32(02):133-139,145.[doi:10.20135/j.issn.1006-8147.2026.02.0133]
　WANG Xingru,LI Xiaomeng,FENG Shanyu.Abnormality of HOIL-1 cleavage promotes colitis-associated colorectal cancer in mice[J].Journal of Tianjin Medical University,2026,32(02):133-139,145.[doi:10.20135/j.issn.1006-8147.2026.02.0133]
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HOIL-1蛋白切割异常促进小鼠结肠炎相关结直肠癌的发生(PDF)

《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
32卷
期数:
2026年02期
页码:
133-139,145
栏目:
肿瘤疾病专题
出版日期:
2026-03-20

文章信息/Info

Title:
Abnormality of HOIL-1 cleavage promotes colitis-associated colorectal cancer in mice
文章编号:
1006-8147(2026)02-0133-08
作者:
王幸如; 李晓萌; 冯善宇
（天津医科大学基础医学院免疫学系，天津300070）
Author(s):
WANG Xingru;  LI Xiaomeng;  FENG Shanyu
（Department of Immunology， School of Basic Medical Sciences， Tianjin Medical University， Tianjin 300070， China）
关键词:
结肠炎相关结直肠癌; 血红素氧化IRP2泛素连接酶1; 偶氮甲烷; 葡聚糖硫酸钠; 炎症; 细胞增殖
Keywords:
colitis-associated colorectal cancer;  HOIL-1;  azoxymethane;  dextran sulfate sodium;  inflammation;  cell proliferation
分类号:
R392
DOI:
10.20135/j.issn.1006-8147.2026.02.0133
文献标志码:
A
摘要:
目的：探讨血红素氧化IRP2泛素连接酶1（HOIL-1）切割异常对小鼠结肠炎相关结直肠癌发生的调控作用。方法：采用已构建的HOIL-1蛋白切割异常小鼠（HOIL-1-R/K，R/K）与同源野生型（WT）小鼠相比，通过偶氮甲烷（AOM）/葡聚糖硫酸钠（DSS）联合诱导，建立小鼠结肠炎相关结直肠癌模型，造模期间观察小鼠体重变化。小鼠分组如下：WT对照组（WT AOM+Water组，n=3）、R/K对照组（R/K AOM+Water组，N=3）、WT实验组（WT AOM+DSS组，n=7）、R/K实验组（R/K AOM+DSS组，n=9）。造模结束后评估小鼠结肠成瘤情况并计算小鼠结肠肿瘤体积；HE染色观察小鼠结肠肿瘤组织病理情况；免疫荧光染色观察结肠肿瘤内免疫细胞浸润数量变化；免疫组化染色分析Ki-67水平，判断肿瘤细胞增殖情况；实时定量-PCR（qPCR）检测结肠肿瘤组织中肿瘤坏死因子-α（TNF-α）与趋化因子配体1（CXCL1）的表达。结果：与其他组相比，R/K实验组体重下降更多（F=2.380，P<0.001）；与WT实验组相比，R/K实验组肿瘤体积更大（t=2.258，P<0.05）；病理切片显示，与WT实验组相比，R/K实验组结肠肿瘤分化程度更低；免疫荧光染色显示，与WT实验组相比，R/K实验组结肠肿瘤内的CD14+细胞数量显著升高（t=2.989，P<0.01）；免疫组化染色显示，与WT实验组相比，R/K实验组结肠肿瘤组织Ki-67的表达量更高（t=3.101，P<0.01）；qPCR结果分析显示，与WT对照组比，WT实验组结肠肿瘤组织中的TNF-α和CXCL1 mRNA表达升高（t=11.44、7.022，均P<0.01），与R/K对照组比，R/K实验组结肠肿瘤组织TNF-α（t=5.852，P<0.001）和CXCL1（t=4.813，P<0.01） mRNA表达升高，与WT实验组相比，R/K实验组结肠肿瘤组织CXCL1 mRNA表达水平升高（t=3.174，P<0.05）。结论：HOIL-1蛋白切割异常会增加AOM-DSS诱导的结肠肿瘤组织内单核细胞的数量和肿瘤细胞增殖，促进结肠炎相关结直肠癌的发生。
Abstract:
Objective： To investigate the regulatory effects of abnormal cleavage of heme-oxidized IRP2 ubiquitin ligase 1（HOIL-1） on the development of colitis-associated colorectal cancer in mice. Methods： Mice with abnormal HOIL-1 protein cleavage （HOIL1-R/K， R/K） were used with syngeneic wild-type （WT） mice for comparison. A mouse model of colitis-associated colorectal cancer was established by induction with the combination of azoxymethane （AOM） and dextran sulfate sodium （DSS）， and the changes in the mouse body weight were observed during the model. Mice were divided into four groups as follows： Wild-type （WT） control group （WT AOM+Water group， n=3）， R/K control group （R/K AOM+Water group， n=3）， WT experimental group （WT AOM+DSS group， n=7）， and R/K experimental group （R/K AOM+DSS group， n=9）. After the completion of modeling， the tumorigenesis status in the colon of mice was evaluated， and the volume of colon tumors was calculated. Hematoxylin and eosin （H&E） staining was used to observe the pathological status in the tumor tissue sections. Immunofluorescence staining was employed to assess the changes in the number of infiltrated immune cells in the colon tumors. The level of Ki-67 was examined by immunohistochemical analysis to determine the proliferation of tumor cells. Quantitative real-time polymerase chain reaction （qPCR） was performed to analyze the expressions of tumor necrosis factor-α （TNF-α） and chemokine ligand 1 （CXCL1） in the colon tumor tissues. Results： Compared with the other groups， the R/K experimental group exhibited a more significant body weight loss （F=2.380， P<0.001）. Regarding tumor volume， it was significantly larger in the R/K experimental group than that in the WT experimental group （t=2.258， P<0.05）. Pathological sections revealed that the colon tumors in the R/K experimental group had a lower degree of differentiation than those in the WT experimental group. Immunofluorescence staining demonstrated a significantly increased number of CD14+ cells in the colon tumors of the R/K experimental group compared with the WT experimental group （t=2.989， P<0.01）. Immunohistochemical staining showed a higher expre-ssion level of Ki-67 in the colon tumor tissues of the R/K experimental group than that in the WT experimental group（t=3.101， P< 0.01）. Furthermore， qPCR analysis indicated that compared with the WT control group， the WT experimental group exhibited increased mRNA expression of TNF-α and CXCL1 in colon tumor tissues （t=11.44， 7.022， both P<0.01）； the R/K experimental group showed elevated mRNA expression of TNF-α （t=5.852， P<0.001） and CXCL1 （t=4.813， P<0.01） compared with the R/K control group， and a higher mRNA expression level of CXCL1 in colon tumor tissues than that in the WT experimental group （t=3.174， P<0.05）. Conclusion： Abnormal cleavage of HOIL-1 protein elevates the number of infiltrated monocytes and increases the proliferation of tumor cells in colon tumor tissues under AOM-DSS induction， and ultimately promotes the development of colitis-associated colorectal cancer.

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备注/Memo

备注/Memo:
基金项目 国家自然科学基金青年项目（82002512）
作者简介 王幸如（2000-），女，硕士在读，研究方向：免疫学；通信作者：冯善宇，E-mail：shanefung@tmu.edu.cn。
更新日期/Last Update: 2026-03-20