Silencing circFTO inhibits malignant phenotype through modulating DUSP4 expression in clear cell renal cell carcinoma
Abstract Clear cell renal cell carcinoma (ccRCC) is the most diagnosed malignancy in kidney. Studies on the role of circular RNAs in kidney cancer are increasing. In this study, we employed high throughput sequencing and tissue micro array to detect and verify one of the key circular RNAs, circFTO,...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-09-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-022-01138-7 |
| _version_ | 1811264891745468416 |
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| author | Chen Yang Yiwen Zang Siqi Wu Quan Zhou Yuxi Ou Qiang Ding Hao Wang Zuquan Xiong |
| author_facet | Chen Yang Yiwen Zang Siqi Wu Quan Zhou Yuxi Ou Qiang Ding Hao Wang Zuquan Xiong |
| author_sort | Chen Yang |
| collection | DOAJ |
| description | Abstract Clear cell renal cell carcinoma (ccRCC) is the most diagnosed malignancy in kidney. Studies on the role of circular RNAs in kidney cancer are increasing. In this study, we employed high throughput sequencing and tissue micro array to detect and verify one of the key circular RNAs, circFTO, in ccRCC. The effect of circFTO on the proliferation and invasiveness of ccRCC cells and the corresponding mechanism were studied both in vitro and in vivo via multiple methods. We confirmed that circFTO was up regulated in ccRCC and correlated with a more aggressive phenotype. The up regulated circFTO could sponge and block the function of miR-514b-3p, a reported tumor suppressor, and caused overexpression of DUSP4. DUSP4 was found to lead to KRAS/ERK pathway activation, increased epithelial-mesenchymal transition (EMT) and inhibition of autophagy in ccRCC cells, which in the end boosted the proliferation and invasiveness of ccRCC. We thus concluded that circFTO/miR-514b-3p/DUSP4 axis may play an important role in ccRCC development and could be a potential biomarker and therapeutic target. |
| first_indexed | 2024-04-12T20:12:31Z |
| format | Article |
| id | doaj.art-4b6f4eb093734211ba42f8eaf382f46e |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-04-12T20:12:31Z |
| publishDate | 2022-09-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-4b6f4eb093734211ba42f8eaf382f46e2022-12-22T03:18:12ZengNature Publishing GroupCell Death Discovery2058-77162022-09-018111010.1038/s41420-022-01138-7Silencing circFTO inhibits malignant phenotype through modulating DUSP4 expression in clear cell renal cell carcinomaChen Yang0Yiwen Zang1Siqi Wu2Quan Zhou3Yuxi Ou4Qiang Ding5Hao Wang6Zuquan Xiong7Huashan Hospital, Fudan UniversityHuashan Hospital, Fudan UniversityHuashan Hospital, Fudan UniversityHuashan Hospital, Fudan UniversityHuashan Hospital, Fudan UniversityHuashan Hospital, Fudan UniversityHuashan Hospital, Fudan UniversityHuashan Hospital, Fudan UniversityAbstract Clear cell renal cell carcinoma (ccRCC) is the most diagnosed malignancy in kidney. Studies on the role of circular RNAs in kidney cancer are increasing. In this study, we employed high throughput sequencing and tissue micro array to detect and verify one of the key circular RNAs, circFTO, in ccRCC. The effect of circFTO on the proliferation and invasiveness of ccRCC cells and the corresponding mechanism were studied both in vitro and in vivo via multiple methods. We confirmed that circFTO was up regulated in ccRCC and correlated with a more aggressive phenotype. The up regulated circFTO could sponge and block the function of miR-514b-3p, a reported tumor suppressor, and caused overexpression of DUSP4. DUSP4 was found to lead to KRAS/ERK pathway activation, increased epithelial-mesenchymal transition (EMT) and inhibition of autophagy in ccRCC cells, which in the end boosted the proliferation and invasiveness of ccRCC. We thus concluded that circFTO/miR-514b-3p/DUSP4 axis may play an important role in ccRCC development and could be a potential biomarker and therapeutic target.https://doi.org/10.1038/s41420-022-01138-7 |
| spellingShingle | Chen Yang Yiwen Zang Siqi Wu Quan Zhou Yuxi Ou Qiang Ding Hao Wang Zuquan Xiong Silencing circFTO inhibits malignant phenotype through modulating DUSP4 expression in clear cell renal cell carcinoma Cell Death Discovery |
| title | Silencing circFTO inhibits malignant phenotype through modulating DUSP4 expression in clear cell renal cell carcinoma |
| title_full | Silencing circFTO inhibits malignant phenotype through modulating DUSP4 expression in clear cell renal cell carcinoma |
| title_fullStr | Silencing circFTO inhibits malignant phenotype through modulating DUSP4 expression in clear cell renal cell carcinoma |
| title_full_unstemmed | Silencing circFTO inhibits malignant phenotype through modulating DUSP4 expression in clear cell renal cell carcinoma |
| title_short | Silencing circFTO inhibits malignant phenotype through modulating DUSP4 expression in clear cell renal cell carcinoma |
| title_sort | silencing circfto inhibits malignant phenotype through modulating dusp4 expression in clear cell renal cell carcinoma |
| url | https://doi.org/10.1038/s41420-022-01138-7 |
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