A Novel ZNF304/miR-183-5p/FOXO4 Pathway Regulates Cell Proliferation in Clear Cell Renal Carcinoma
Zinc-finger protein 304 (ZNF304) plays a critical role in silencing genes through transcription, regulating cell survival, proliferation, apoptosis, and differentiation during development. However, the roles of transcription factor ZNF304 and its clinical significance in clear cell renal carcinoma (...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.710525/full |
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| author | Li-Xin Ren Bo-Wen Zeng Meng Zhu An-Ning Zhao Bei Shi Hong Zhang Dan-Dan Wang Jun-Fei Gu Zhan Yang |
| author_facet | Li-Xin Ren Bo-Wen Zeng Meng Zhu An-Ning Zhao Bei Shi Hong Zhang Dan-Dan Wang Jun-Fei Gu Zhan Yang |
| author_sort | Li-Xin Ren |
| collection | DOAJ |
| description | Zinc-finger protein 304 (ZNF304) plays a critical role in silencing genes through transcription, regulating cell survival, proliferation, apoptosis, and differentiation during development. However, the roles of transcription factor ZNF304 and its clinical significance in clear cell renal carcinoma (ccRCC) remain unclear. In this study, we found that the expression of ZNF304 was downregulated in ccRCC tissues. Lower levels of ZNF304 were correlated with poor survival. Downregulation of ZNF304 promoted ccRCC cell growth in vitro, whereas overexpression of ZNF304 inhibited growth. Our results indicated that miR-183-5p/FOXO4 mediated ZNF304 regulation of cell growth. Interestingly, we revealed that ZNF304 promoted FOXO4 expression in ccRCC cells. Mechanistically, ZNF304 binds to miR-183 promoter and inhibits miR-183-5p transcription. Furthermore, the expression of miR-183-5p wes increased in ccRCC tissues, and the upregulation of miR-183-5p was related to the poor prognosis of ccRCC patients. miR-183-5p upregulation repressed the expression of FOXO4 and promoted ccRCC progression. These results demonstrated that ZNF304/miR-183-5p/FOXO4 axis played essential role in promoting ccRCC progression, which suggests that disruption of this axis may be a potential therapeutic target in ccRCC. |
| first_indexed | 2024-12-17T13:51:37Z |
| format | Article |
| id | doaj.art-11b98bb2794448168ba8b4733d7b5020 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-17T13:51:37Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-11b98bb2794448168ba8b4733d7b50202022-12-21T21:46:02ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-10-011110.3389/fonc.2021.710525710525A Novel ZNF304/miR-183-5p/FOXO4 Pathway Regulates Cell Proliferation in Clear Cell Renal CarcinomaLi-Xin Ren0Bo-Wen Zeng1Meng Zhu2An-Ning Zhao3Bei Shi4Hong Zhang5Dan-Dan Wang6Jun-Fei Gu7Zhan Yang8Department of Urology, The Second Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Urology, Affiliated Hospital of Sergeant School of Army Medical University, Shijiazhuang, ChinaDepartment of Urology, The Second Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Urology, The Second Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Urology, The Second Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Urology, The Second Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Urology, The Second Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Urology, The Second Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Urology, The Second Hospital of Hebei Medical University, Shijiazhuang, ChinaZinc-finger protein 304 (ZNF304) plays a critical role in silencing genes through transcription, regulating cell survival, proliferation, apoptosis, and differentiation during development. However, the roles of transcription factor ZNF304 and its clinical significance in clear cell renal carcinoma (ccRCC) remain unclear. In this study, we found that the expression of ZNF304 was downregulated in ccRCC tissues. Lower levels of ZNF304 were correlated with poor survival. Downregulation of ZNF304 promoted ccRCC cell growth in vitro, whereas overexpression of ZNF304 inhibited growth. Our results indicated that miR-183-5p/FOXO4 mediated ZNF304 regulation of cell growth. Interestingly, we revealed that ZNF304 promoted FOXO4 expression in ccRCC cells. Mechanistically, ZNF304 binds to miR-183 promoter and inhibits miR-183-5p transcription. Furthermore, the expression of miR-183-5p wes increased in ccRCC tissues, and the upregulation of miR-183-5p was related to the poor prognosis of ccRCC patients. miR-183-5p upregulation repressed the expression of FOXO4 and promoted ccRCC progression. These results demonstrated that ZNF304/miR-183-5p/FOXO4 axis played essential role in promoting ccRCC progression, which suggests that disruption of this axis may be a potential therapeutic target in ccRCC.https://www.frontiersin.org/articles/10.3389/fonc.2021.710525/fullzinc-finger protein 304proliferationFOXO4miR-183-5pclear cell renal carcinoma (ccRCC) |
| spellingShingle | Li-Xin Ren Bo-Wen Zeng Meng Zhu An-Ning Zhao Bei Shi Hong Zhang Dan-Dan Wang Jun-Fei Gu Zhan Yang A Novel ZNF304/miR-183-5p/FOXO4 Pathway Regulates Cell Proliferation in Clear Cell Renal Carcinoma Frontiers in Oncology zinc-finger protein 304 proliferation FOXO4 miR-183-5p clear cell renal carcinoma (ccRCC) |
| title | A Novel ZNF304/miR-183-5p/FOXO4 Pathway Regulates Cell Proliferation in Clear Cell Renal Carcinoma |
| title_full | A Novel ZNF304/miR-183-5p/FOXO4 Pathway Regulates Cell Proliferation in Clear Cell Renal Carcinoma |
| title_fullStr | A Novel ZNF304/miR-183-5p/FOXO4 Pathway Regulates Cell Proliferation in Clear Cell Renal Carcinoma |
| title_full_unstemmed | A Novel ZNF304/miR-183-5p/FOXO4 Pathway Regulates Cell Proliferation in Clear Cell Renal Carcinoma |
| title_short | A Novel ZNF304/miR-183-5p/FOXO4 Pathway Regulates Cell Proliferation in Clear Cell Renal Carcinoma |
| title_sort | novel znf304 mir 183 5p foxo4 pathway regulates cell proliferation in clear cell renal carcinoma |
| topic | zinc-finger protein 304 proliferation FOXO4 miR-183-5p clear cell renal carcinoma (ccRCC) |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.710525/full |
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