Downregulation of MTHFD2 Inhibits Proliferation and Enhances Chemosensitivity in Hepatocellular Carcinoma via PI3K/AKT Pathway
Background: Despite the substantial impact of methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) on cancer progression, its significance in the regulation of hepatocellular carcinoma (HCC) cell proliferation and chemosensitivity remains poorly defined. Methods: We evaluated MTHFD2 expression in a to...
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| Format: | Article |
| Language: | English |
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IMR Press
2024-01-01
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| Series: | Frontiers in Bioscience-Landmark |
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| Online Access: | https://www.imrpress.com/journal/FBL/29/1/10.31083/j.fbl2901035 |
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| author | Jie Wang Ze Yu Yixiao Jiang Ting Le Yixin Wu Ziqi Li Guoqiang Zhang Feiyue Wu Haijie Ma |
| author_facet | Jie Wang Ze Yu Yixiao Jiang Ting Le Yixin Wu Ziqi Li Guoqiang Zhang Feiyue Wu Haijie Ma |
| author_sort | Jie Wang |
| collection | DOAJ |
| description | Background: Despite the substantial impact of methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) on cancer progression, its significance in the regulation of hepatocellular carcinoma (HCC) cell proliferation and chemosensitivity remains poorly defined. Methods: We evaluated MTHFD2 expression in a total of 95 HCC tissues by immunohistochemistry and analyzed the association of MTHFD2 with clinicopathologic features. qRT-PCR and Western blotting were conducted to verify MTHFD2 expression levels. Bioinformatics analysis such as gene set enrichment analysis (GSEA) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were used to predict the signaling pathways involved in MTHFD2. In addition, to investigate the anti-tumor effects of MTHFD2 knockdown, Cell Counting Kit-8 (CCK-8) and EdU assays were used. Results: We found that MTHFD2 was frequently upregulated in HCC, and the combination of increased expression of MTHFD2 and Ki67 was associated with poor HCC prognosis. MTHFD2 knockdown significantly inhibited HCC cell proliferation and effectively sensitized HCC cells to sorafenib and lenvatinib. PI3K/AKT pathway was involved in MTHFD2-mediated modulation of proliferation and chemosensitivity. Conclusions: These findings indicate that MTHFD2 plays an important role in proliferation and chemosensitivity of HCC, indicating that it may serve as a novel pharmacological target for improving HCC therapy. |
| first_indexed | 2024-03-08T09:36:38Z |
| format | Article |
| id | doaj.art-3c920926a0a244b6a255159726f10408 |
| institution | Directory Open Access Journal |
| issn | 2768-6701 |
| language | English |
| last_indexed | 2024-03-08T09:36:38Z |
| publishDate | 2024-01-01 |
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| record_format | Article |
| series | Frontiers in Bioscience-Landmark |
| spelling | doaj.art-3c920926a0a244b6a255159726f104082024-01-30T07:44:35ZengIMR PressFrontiers in Bioscience-Landmark2768-67012024-01-012913510.31083/j.fbl2901035S2768-6701(23)01128-0Downregulation of MTHFD2 Inhibits Proliferation and Enhances Chemosensitivity in Hepatocellular Carcinoma via PI3K/AKT PathwayJie Wang0Ze Yu1Yixiao Jiang2Ting Le3Yixin Wu4Ziqi Li5Guoqiang Zhang6Feiyue Wu7Haijie Ma8Cellular and Molecular Biology Laboratory, Zhoushan Hospital, Wenzhou Medical University, 316021 Zhoushan, Zhejiang, ChinaCellular and Molecular Biology Laboratory, Zhoushan Hospital, Wenzhou Medical University, 316021 Zhoushan, Zhejiang, ChinaDepartment of General Surgery, Zhoushan Hospital, 316021 Zhoushan, Zhejiang, ChinaCellular and Molecular Biology Laboratory, Zhoushan Hospital, Wenzhou Medical University, 316021 Zhoushan, Zhejiang, ChinaCellular and Molecular Biology Laboratory, Zhoushan Hospital, Wenzhou Medical University, 316021 Zhoushan, Zhejiang, ChinaCellular and Molecular Biology Laboratory, Zhoushan Hospital, Wenzhou Medical University, 316021 Zhoushan, Zhejiang, ChinaDepartment of General Surgery, Zhoushan Hospital, 316021 Zhoushan, Zhejiang, ChinaDepartment of Pharmacy, Zhoushan Hospital, 316021 Zhoushan, Zhejiang, ChinaCellular and Molecular Biology Laboratory, Zhoushan Hospital, Wenzhou Medical University, 316021 Zhoushan, Zhejiang, ChinaBackground: Despite the substantial impact of methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) on cancer progression, its significance in the regulation of hepatocellular carcinoma (HCC) cell proliferation and chemosensitivity remains poorly defined. Methods: We evaluated MTHFD2 expression in a total of 95 HCC tissues by immunohistochemistry and analyzed the association of MTHFD2 with clinicopathologic features. qRT-PCR and Western blotting were conducted to verify MTHFD2 expression levels. Bioinformatics analysis such as gene set enrichment analysis (GSEA) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were used to predict the signaling pathways involved in MTHFD2. In addition, to investigate the anti-tumor effects of MTHFD2 knockdown, Cell Counting Kit-8 (CCK-8) and EdU assays were used. Results: We found that MTHFD2 was frequently upregulated in HCC, and the combination of increased expression of MTHFD2 and Ki67 was associated with poor HCC prognosis. MTHFD2 knockdown significantly inhibited HCC cell proliferation and effectively sensitized HCC cells to sorafenib and lenvatinib. PI3K/AKT pathway was involved in MTHFD2-mediated modulation of proliferation and chemosensitivity. Conclusions: These findings indicate that MTHFD2 plays an important role in proliferation and chemosensitivity of HCC, indicating that it may serve as a novel pharmacological target for improving HCC therapy.https://www.imrpress.com/journal/FBL/29/1/10.31083/j.fbl2901035mthfd2proliferationchemosensitivityhccki-67 |
| spellingShingle | Jie Wang Ze Yu Yixiao Jiang Ting Le Yixin Wu Ziqi Li Guoqiang Zhang Feiyue Wu Haijie Ma Downregulation of MTHFD2 Inhibits Proliferation and Enhances Chemosensitivity in Hepatocellular Carcinoma via PI3K/AKT Pathway Frontiers in Bioscience-Landmark mthfd2 proliferation chemosensitivity hcc ki-67 |
| title | Downregulation of MTHFD2 Inhibits Proliferation and Enhances Chemosensitivity in Hepatocellular Carcinoma via PI3K/AKT Pathway |
| title_full | Downregulation of MTHFD2 Inhibits Proliferation and Enhances Chemosensitivity in Hepatocellular Carcinoma via PI3K/AKT Pathway |
| title_fullStr | Downregulation of MTHFD2 Inhibits Proliferation and Enhances Chemosensitivity in Hepatocellular Carcinoma via PI3K/AKT Pathway |
| title_full_unstemmed | Downregulation of MTHFD2 Inhibits Proliferation and Enhances Chemosensitivity in Hepatocellular Carcinoma via PI3K/AKT Pathway |
| title_short | Downregulation of MTHFD2 Inhibits Proliferation and Enhances Chemosensitivity in Hepatocellular Carcinoma via PI3K/AKT Pathway |
| title_sort | downregulation of mthfd2 inhibits proliferation and enhances chemosensitivity in hepatocellular carcinoma via pi3k akt pathway |
| topic | mthfd2 proliferation chemosensitivity hcc ki-67 |
| url | https://www.imrpress.com/journal/FBL/29/1/10.31083/j.fbl2901035 |
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