MUTYH is associated with hepatocarcinogenesis in a non-alcoholic steatohepatitis mouse model
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 t...
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Nature Portfolio
2021
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oai:doaj.org-article:69299cb1a36c415897cf85463ac68c382021-12-02T14:26:47ZMUTYH is associated with hepatocarcinogenesis in a non-alcoholic steatohepatitis mouse model10.1038/s41598-021-83138-82045-2322https://doaj.org/article/69299cb1a36c415897cf85463ac68c382021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83138-8https://doaj.org/toc/2045-2322Abstract 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.Hiroki SakamotoKoji MiyanishiShingo TanakaRyo ItoKota HamaguchiAkira SakuradaMasanori SatoTomohiro KuboTakahiro OsugaKazuyuki MuraseKohichi TakadaYusaku NakabeppuMasayoshi KobuneJunji KatoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021) |
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Medicine R Science Q |
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Medicine R Science Q Hiroki Sakamoto Koji Miyanishi Shingo Tanaka Ryo Ito Kota Hamaguchi Akira Sakurada Masanori Sato Tomohiro Kubo Takahiro Osuga Kazuyuki Murase Kohichi Takada Yusaku Nakabeppu Masayoshi Kobune Junji Kato MUTYH is associated with hepatocarcinogenesis in a non-alcoholic steatohepatitis mouse model |
| description |
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. |
| format |
article |
| author |
Hiroki Sakamoto Koji Miyanishi Shingo Tanaka Ryo Ito Kota Hamaguchi Akira Sakurada Masanori Sato Tomohiro Kubo Takahiro Osuga Kazuyuki Murase Kohichi Takada Yusaku Nakabeppu Masayoshi Kobune Junji Kato |
| author_facet |
Hiroki Sakamoto Koji Miyanishi Shingo Tanaka Ryo Ito Kota Hamaguchi Akira Sakurada Masanori Sato Tomohiro Kubo Takahiro Osuga Kazuyuki Murase Kohichi Takada Yusaku Nakabeppu Masayoshi Kobune Junji Kato |
| author_sort |
Hiroki Sakamoto |
| title |
MUTYH is associated with hepatocarcinogenesis in a non-alcoholic steatohepatitis mouse model |
| title_short |
MUTYH is associated with hepatocarcinogenesis in a non-alcoholic steatohepatitis mouse model |
| title_full |
MUTYH is associated with hepatocarcinogenesis in a non-alcoholic steatohepatitis mouse model |
| title_fullStr |
MUTYH is associated with hepatocarcinogenesis in a non-alcoholic steatohepatitis mouse model |
| title_full_unstemmed |
MUTYH is associated with hepatocarcinogenesis in a non-alcoholic steatohepatitis mouse model |
| title_sort |
mutyh is associated with hepatocarcinogenesis in a non-alcoholic steatohepatitis mouse model |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/69299cb1a36c415897cf85463ac68c38 |
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