The Mutual Inhibition of FoxO1 and SREBP-1c Regulated the Progression of Hepatoblastoma by Regulating Fatty Acid Metabolism
Background. Hepatoblastoma (HB) is the most common liver malignancy in pediatrics, but the treatment for this disease is minimal. This study is aimed at exploring the effect of FoxO1 and SREBP-1c on HB and their mechanism. Methods. FoxO1, SREBP-1c, FASN, ACLY, ACC, and MAGL expressions in tissue sam...
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Wiley
2021-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2021/5754592 |
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| author | Yu Hu Hongyan Zai Wei Jiang Zhenglin Ou Yuanbing Yao Qin Zhu |
| author_facet | Yu Hu Hongyan Zai Wei Jiang Zhenglin Ou Yuanbing Yao Qin Zhu |
| author_sort | Yu Hu |
| collection | DOAJ |
| description | Background. Hepatoblastoma (HB) is the most common liver malignancy in pediatrics, but the treatment for this disease is minimal. This study is aimed at exploring the effect of FoxO1 and SREBP-1c on HB and their mechanism. Methods. FoxO1, SREBP-1c, FASN, ACLY, ACC, and MAGL expressions in tissue samples were detected by RT-qPCR and WB. IHC was utilized to measure FASN content. Overexpression and knockdown of FoxO1 and sSREBP-1c were performed on Huh-6 cells. Cell proliferation, migration, and invasion were examined by CCK8, scratch, and transwell assay. ELISA was performed to test the ATP, FAO, NEFA, and Acetyl-CoA contents. ChIP was used to detect the interaction between SREBP-1c protein and the FoxO1 gene. In vivo tumorigenesis was conducted on mice. The morphology of tumor tissue sections was observed by HE staining. Results. FoxO1 expression was downregulated in HB tissue, while the expressions of SREBP-1c, FASN, ACLY, ACC, and MAGL were upregulated. In Huh-6 cells and mouse tumor tissues, FoxO1 knockdown resulted in increased cell proliferation, migration, and invasion and active fatty acid metabolism. On the contrary, after the knockdown of SREBP-1c, cell proliferation, migration, and invasion were weakened, and fatty acid metabolism was significantly reduced. SREBP-1c interacted with the promoter of the FoxO1 gene. When FoxO1 was knocked down, the tumor tissue was more closely packed. After the knockdown of the SREBP-1c gene, the structure of tumor cells was deformed. Conclusion. FoxO1 and SREBP-1c inhibited each other in HB, leading to the increase of intracellular fatty acid metabolism, and ultimately facilitated the development of HB. |
| format | Article |
| id | doaj-art-d5328cd0b87444fab354ee8965c53f00 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-d5328cd0b87444fab354ee8965c53f002025-02-03T01:08:48ZengWileyMediators of Inflammation0962-93511466-18612021-01-01202110.1155/2021/57545925754592The Mutual Inhibition of FoxO1 and SREBP-1c Regulated the Progression of Hepatoblastoma by Regulating Fatty Acid MetabolismYu Hu0Hongyan Zai1Wei Jiang2Zhenglin Ou3Yuanbing Yao4Qin Zhu5Department of General Surgery, Xiangya Hospital, Central South University, Changsha, 410008, ChinaDepartment of General Surgery, Xiangya Hospital, Central South University, Changsha, 410008, ChinaDepartment of General Surgery, Xiangya Hospital, Central South University, Changsha, 410008, ChinaDepartment of General Surgery, Xiangya Hospital, Central South University, Changsha, 410008, ChinaDepartment of General Surgery, Xiangya Hospital, Central South University, Changsha, 410008, ChinaDepartment of General Surgery, Xiangya Hospital, Central South University, Changsha, 410008, ChinaBackground. Hepatoblastoma (HB) is the most common liver malignancy in pediatrics, but the treatment for this disease is minimal. This study is aimed at exploring the effect of FoxO1 and SREBP-1c on HB and their mechanism. Methods. FoxO1, SREBP-1c, FASN, ACLY, ACC, and MAGL expressions in tissue samples were detected by RT-qPCR and WB. IHC was utilized to measure FASN content. Overexpression and knockdown of FoxO1 and sSREBP-1c were performed on Huh-6 cells. Cell proliferation, migration, and invasion were examined by CCK8, scratch, and transwell assay. ELISA was performed to test the ATP, FAO, NEFA, and Acetyl-CoA contents. ChIP was used to detect the interaction between SREBP-1c protein and the FoxO1 gene. In vivo tumorigenesis was conducted on mice. The morphology of tumor tissue sections was observed by HE staining. Results. FoxO1 expression was downregulated in HB tissue, while the expressions of SREBP-1c, FASN, ACLY, ACC, and MAGL were upregulated. In Huh-6 cells and mouse tumor tissues, FoxO1 knockdown resulted in increased cell proliferation, migration, and invasion and active fatty acid metabolism. On the contrary, after the knockdown of SREBP-1c, cell proliferation, migration, and invasion were weakened, and fatty acid metabolism was significantly reduced. SREBP-1c interacted with the promoter of the FoxO1 gene. When FoxO1 was knocked down, the tumor tissue was more closely packed. After the knockdown of the SREBP-1c gene, the structure of tumor cells was deformed. Conclusion. FoxO1 and SREBP-1c inhibited each other in HB, leading to the increase of intracellular fatty acid metabolism, and ultimately facilitated the development of HB.http://dx.doi.org/10.1155/2021/5754592 |
| spellingShingle | Yu Hu Hongyan Zai Wei Jiang Zhenglin Ou Yuanbing Yao Qin Zhu The Mutual Inhibition of FoxO1 and SREBP-1c Regulated the Progression of Hepatoblastoma by Regulating Fatty Acid Metabolism Mediators of Inflammation |
| title | The Mutual Inhibition of FoxO1 and SREBP-1c Regulated the Progression of Hepatoblastoma by Regulating Fatty Acid Metabolism |
| title_full | The Mutual Inhibition of FoxO1 and SREBP-1c Regulated the Progression of Hepatoblastoma by Regulating Fatty Acid Metabolism |
| title_fullStr | The Mutual Inhibition of FoxO1 and SREBP-1c Regulated the Progression of Hepatoblastoma by Regulating Fatty Acid Metabolism |
| title_full_unstemmed | The Mutual Inhibition of FoxO1 and SREBP-1c Regulated the Progression of Hepatoblastoma by Regulating Fatty Acid Metabolism |
| title_short | The Mutual Inhibition of FoxO1 and SREBP-1c Regulated the Progression of Hepatoblastoma by Regulating Fatty Acid Metabolism |
| title_sort | mutual inhibition of foxo1 and srebp 1c regulated the progression of hepatoblastoma by regulating fatty acid metabolism |
| url | http://dx.doi.org/10.1155/2021/5754592 |
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