文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期，新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

MUTYH 与非酒精性脂肪性肝炎小鼠模型中的肝癌发生有关。

MUTYH is associated with hepatocarcinogenesis in a non-alcoholic steatohepatitis mouse model.

机构信息

Department of Medical Oncology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan.

Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.

出版信息

Sci Rep. 2021 Feb 11;11(1):3599. doi: 10.1038/s41598-021-83138-8.

DOI:10.1038/s41598-021-83138-8
PMID:33574380
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7878918/
Abstract

Non-alcoholic steatohepatitis (NASH)-related HCC is associated with oxidative stress. However, the mechanisms underlying the development of NASH-related HCC is unclear. MUTYH is one of the enzymes that is involved in repair of oxidative DNA damage. The aim of this study was to investigate the association between MUTYH and NASH-related hepatocarcinogenesis. MUTYH wild-type (Mutyh), heterozygous (Mutyh), and MUTYH-null (Mutyh) mice were fed a high-fat high-cholesterol (HFHC) diet or HFHC + high iron diet (20 mice per group) for 9 months. Five of 20 Mutyh mice fed an HFHC + high iron diet developed liver tumors, and they developed more liver tumors than other groups (especially vs. Mutyh fed an HFHC diet, P = 0.0168). Immunohistochemical analysis revealed significantly higher accumulation of oxidative stress markers in mice fed an HFHC + high iron diet. The gene expression profiles in the non-tumorous hepatic tissues were compared between wild-type mice that developed no liver tumors and MUTYH-null mice that developed liver tumors. Gene Set Enrichment Analysis identified the involvement of the Wnt/β-catenin signaling pathway and increased expression of c-Myc in MUTYH-null liver. These findings suggest that MUTYH deficiency is associated with hepatocarcinogenesis in patients with NASH with hepatic iron accumulation.

摘要

非酒精性脂肪性肝炎（NASH）相关 HCC 与氧化应激有关。然而，NASH 相关 HCC 的发展机制尚不清楚。MUTYH 是参与修复氧化 DNA 损伤的酶之一。本研究旨在探讨 MUTYH 与 NASH 相关肝癌发生的关系。MUTYH 野生型（Mutyh）、杂合型（Mutyh）和 MUTYH 缺失型（Mutyh）小鼠分别用高脂肪高胆固醇（HFHC）饮食或 HFHC+高铁饮食（每组 20 只）喂养 9 个月。20 只 Mutyh 喂养 HFHC+高铁饮食的小鼠中有 5 只发生了肝肿瘤，其肿瘤发生率高于其他组（尤其是与 HFHC 饮食喂养的 Mutyh 相比，P=0.0168）。免疫组化分析显示，HFHC+高铁饮食喂养的小鼠中氧化应激标志物的积累明显更高。在未发生肝肿瘤的野生型小鼠和发生肝肿瘤的 MUTYH 缺失型小鼠的非肿瘤性肝组织中比较基因表达谱。基因集富集分析鉴定了 Wnt/β-catenin 信号通路的参与和 MUTYH 缺失型肝中 c-Myc 的表达增加。这些发现表明，MUTYH 缺失与伴有肝铁蓄积的 NASH 患者的肝癌发生有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e07/7878918/bc0f3066bdc7/41598_2021_83138_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e07/7878918/d3a0adb12609/41598_2021_83138_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e07/7878918/b5ecad85bbd8/41598_2021_83138_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e07/7878918/37703bc5bcd9/41598_2021_83138_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e07/7878918/ffdeb5e56161/41598_2021_83138_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e07/7878918/ec20e19123d9/41598_2021_83138_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e07/7878918/bc0f3066bdc7/41598_2021_83138_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e07/7878918/d3a0adb12609/41598_2021_83138_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e07/7878918/b5ecad85bbd8/41598_2021_83138_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e07/7878918/37703bc5bcd9/41598_2021_83138_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e07/7878918/ffdeb5e56161/41598_2021_83138_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e07/7878918/ec20e19123d9/41598_2021_83138_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e07/7878918/bc0f3066bdc7/41598_2021_83138_Fig6_HTML.jpg

相似文献

[1]
MUTYH is associated with hepatocarcinogenesis in a non-alcoholic steatohepatitis mouse model.

Sci Rep. 2021-2-11

[2]
An intronic single nucleotide polymorphism in the MUTYH gene is associated with increased risk for HCV-induced hepatocellular carcinoma.

Free Radic Biol Med. 2018-9-13

[3]
Role of CC chemokine receptor 9 in the progression of murine and human non-alcoholic steatohepatitis.

J Hepatol. 2021-3

[4]
Notch activity characterizes a common hepatocellular carcinoma subtype with unique molecular and clinicopathologic features.

J Hepatol. 2021-3

[5]
STARD1 promotes NASH-driven HCC by sustaining the generation of bile acids through the alternative mitochondrial pathway.

J Hepatol. 2021-6

[6]
MicroRNA expression analysis in high fat diet-induced NAFLD-NASH-HCC progression: study on C57BL/6J mice.

BMC Cancer. 2016-1-5

[7]
Sex hormone-binding globulin suppresses NAFLD-triggered hepatocarcinogenesis after menopause.

Carcinogenesis. 2019-8-22

[8]
Oxidative stress and Liver X Receptor agonist induce hepatocellular carcinoma in Non-alcoholic steatohepatitis model.

J Gastroenterol Hepatol. 2021-3

[9]
MCLR-elicited hepatic fibrosis and carcinogenic gene expression changes persist in rats with diet-induced nonalcoholic steatohepatitis through a 4-week recovery period.

Toxicology. 2021-12

[10]
Hepatocellular carcinoma and non-alcoholic steatohepatitis: The state of play.

World J Gastroenterol. 2016-2-28

引用本文的文献

[1]
Exploring the Role of Metabolic Hyperferritinaemia (MHF) in Steatotic Liver Disease (SLD) and Hepatocellular Carcinoma (HCC).

Cancers (Basel). 2025-2-28

[2]
Reassessing the roles of oxidative DNA base lesion 8-oxoGua and repair enzyme OGG1 in tumorigenesis.

J Biomed Sci. 2025-1-1

[3]
DNA damage repair-related gene signature for identifying the immune status and predicting the prognosis of hepatocellular carcinoma.

Sci Rep. 2023-11-3

[4]
Association between Hepatic Oxidative Stress Related Factors and Activation of Wnt/β-Catenin Signaling in NAFLD-Induced Hepatocellular Carcinoma.

Cancers (Basel). 2022-4-20

[5]
Reactive oxygen species in cancer: Current findings and future directions.

Cancer Sci. 2021-10

本文引用的文献

[1]
Mesenchymal iron deposition is associated with adverse long-term outcome in non-alcoholic fatty liver disease.

Liver Int. 2020-8

[2]
An intronic single nucleotide polymorphism in the MUTYH gene is associated with increased risk for HCV-induced hepatocellular carcinoma.

Free Radic Biol Med. 2018-9-13

[3]
High expression of nucleoporin 133 mRNA in bone marrow CD138+ cells is a poor prognostic factor in multiple myeloma.

Oncotarget. 2018-5-18

[4]
Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma.

Cell. 2017-6-15

[5]
Integrative transcriptomic analysis of NAFLD animal model reveals dysregulated genes and pathways in metabolism.

Gene. 2016-12-20

[6]
Comparison of Gene Expression Patterns Between Mouse Models of Nonalcoholic Fatty Liver Disease and Liver Tissues From Patients.

Gastroenterology. 2016-6-16

[7]
Oxidative stress as an iceberg in carcinogenesis and cancer biology.

Arch Biochem Biophys. 2016-4-1

[8]
Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer.

Nat Genet. 2016-4-11

[9]
Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes.

Hepatology. 2016-2-22

[10]
Increased duodenal iron absorption through up-regulation of divalent metal transporter 1 from enhancement of iron regulatory protein 1 activity in patients with nonalcoholic steatohepatitis.

Hepatology. 2015-4-8

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索