Characterization of mouse embryonic fibroblasts derived fromRassf6knockout mice shows the implication of Rassf6 in the regulation of NF‐κB signaling
| Autor: | Yutaka Hata, Masanobu Kitagawa, Mayu Morishita, Yuichi Hiraoka, Kohei Yamamoto, Kyohei Niimura, Masami Kitamura, Hiroaki Iwasa, Hiroshi Nishina, Junichi Maruyama, Kyoko Arimoto-Matsuzaki, Norio Miyamura |
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| Rok vydání: | 2021 |
| Předmět: |
Mice
Knockout Cell cycle checkpoint DNA repair NF-kappa B Apoptosis NF-κB Cell Biology Fibroblasts Biology medicine.disease_cause Embryonic stem cell Cell biology Mice chemistry.chemical_compound chemistry Knockout mouse Gene expression Genetics medicine Animals Tumor Suppressor Protein p53 Apoptosis Regulatory Proteins Carcinogenesis Monomeric GTP-Binding Proteins |
| Zdroj: | Genes to Cells. 26:999-1013 |
| ISSN: | 1365-2443 1356-9597 |
| Popis: | RASSF6 is a member of the tumor suppressor Ras-association domain family (RASSF) proteins. We have reported using human cancer cell lines that RASSF6 induces apoptosis and cell cycle arrest via p53 and plays tumor-suppressive roles. In this study, we generated Rassf6 knockout mice by CRISPR/Cas technology. Contrary to our expectation, Rassf6 knockout mice were apparently healthy. However, Rassf6-null mouse embryonic fibroblasts (MEF) were resistant against ultraviolet (UV)-induced apoptosis/cell cycle arrest and senescence. UV-induced p53-target gene expression was compromised and DNA repair was delayed in Rassf6-null MEF. More importantly, KRAS active mutant promoted the colony formation of Rassf6-null MEF but not the wild-type MEF. RNA sequencing analysis revealed that NF-κB signaling was enhanced in Rassf6-null MEF. Consistently, 7,12-Dimethylbenz(a)anthracene (DMBA) induced skin inflammation in Rassf6 knockout mice more remarkably than in the wild-type mice. Hence, Rassf6 deficiency not only compromises p53 function but also enhances NF-κB signaling to lead to oncogenesis. |
| Databáze: | OpenAIRE |
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