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

被引：5

作者：

Sakamoto, Hiroki ^{[1
]}

Miyanishi, Koji ^{[1
]}

Tanaka, Shingo ^{[1
]}

Ito, Ryo ^{[1
]}

Hamaguchi, Kota ^{[1
]}

Sakurada, Akira ^{[1
]}

Sato, Masanori ^{[1
]}

Kubo, Tomohiro ^{[1
]}

Osuga, Takahiro ^{[1
]}

Murase, Kazuyuki ^{[1
]}

Takada, Kohichi ^{[1
]}

Nakabeppu, Yusaku ^{[3
]}

Kobune, Masayoshi ^{[2
]}

Kato, Junji ^{[1
]}

机构：

[1] Sapporo Med Univ, Sch Med, Dept Med Oncol, Chuo Ku, South 1,West-16, Sapporo, Hokkaido 0608543, Japan

[2] Sapporo Med Univ, Sch Med, Dept Hematol, Chuo Ku, South 1,West-16, Sapporo, Hokkaido 0608543, Japan

[3] Kyushu Univ, Med Inst Bioregulat, Dept Immunobiol & Neurosci, Div Neurofunct Genom,Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan

来源：

SCIENTIFIC REPORTS | 2021年 / 11卷 / 01期

关键词：

SERUM THIOREDOXIN LEVELS; FATTY LIVER-DISEASE; CHRONIC HEPATITIS-C; HEPATOCELLULAR-CARCINOMA; COLORECTAL-CANCER; OXIDATIVE STRESS; MUTATIONS; RISK; MICE; PROGRESSION;

D O I：

10.1038/s41598-021-83138-8

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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/beta -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.

引用

页数：13