ERβ-regulated circATP2B1/miR-204–3p/TWIST1 positive feedback loop facilitates epithelial to mesenchymal transition in clear cell renal cell carcinoma
Background: Our previous studies have shown that estrogen receptor beta (ERβ) can promote the progression of clear cell renal cell carcinoma (ccRCC) by downregulating the expression of circATP2B1 and miR-204–3p. Here, we found that ERβ might promote the epithelial-mesenchymal transition(EMT) of ccRC...
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Elsevier
2025-01-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523324003401 |
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| author | Hu Wang Yilong Gao Fengran Guo Pengfei Zhou Ziyang Ma Kui Chi Jiaqing Ye Hao Sun Xingyu He Bei Shi Yaxuan Wang Zhenwei Han |
| author_facet | Hu Wang Yilong Gao Fengran Guo Pengfei Zhou Ziyang Ma Kui Chi Jiaqing Ye Hao Sun Xingyu He Bei Shi Yaxuan Wang Zhenwei Han |
| author_sort | Hu Wang |
| collection | DOAJ |
| description | Background: Our previous studies have shown that estrogen receptor beta (ERβ) can promote the progression of clear cell renal cell carcinoma (ccRCC) by downregulating the expression of circATP2B1 and miR-204–3p. Here, we found that ERβ might promote the epithelial-mesenchymal transition(EMT) of ccRCC by modulating the circATP2B1/miR-204–3p/TWIST1(Twist family basic helix-loop-helix transcription factor 1) signaling pathway. Methods: We utilized bioinformatics analysis to determine the clinical significance of TWIST1 in ccRCC. The expression of TWIST1 in ccRCC tissues and cells was examined using immunohistochemistry, real-time quantitative polymerase chain reaction and western blotting assay. Chromatin Immunoprecipitation assay were conducted to validate the relationship between ERβ and TWIST1. Luciferase reporter gene assays were employed to validate the binding targets of TWIST1 and miR-204–3p. The role of TWIST1 in ccRCC was studied through in vitro and in vivo experiments. Transwell assays and wound healing assays were used to assess the impact of TWIST1 on the invasive and migratory abilities of ccRCC cells. Results: Mechanism analysis revealed that miR-204–3p can inhibit TWIST1 by targeting its 3′ untranslated region. Additionally, TWIST1 can promote ERβ transcription by directly binding to transcription factor binding site in the ERβ promoter region, forming a positive feedback loop. These in vitro data were further validated in an in vivo mouse model. Importantly, analysis of data from the TCGA-KIRC database further confirmed the above in vitro/in vivo findings. Conclusions: Together, our results suggest that ERβ/circATP2B1/miR-204–3p/TWIST1 can promote EMT by forming a positive feedback loop, thus promoting the progression of ccRCC. Targeting this newly identified signaling pathway may more effectively control the progression of ccRCC. |
| format | Article |
| id | doaj-art-9fe0a7cea93b4ef2aeccb146216b589e |
| institution | OA Journals |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-9fe0a7cea93b4ef2aeccb146216b589e2025-08-20T02:30:34ZengElsevierTranslational Oncology1936-52332025-01-015110221310.1016/j.tranon.2024.102213ERβ-regulated circATP2B1/miR-204–3p/TWIST1 positive feedback loop facilitates epithelial to mesenchymal transition in clear cell renal cell carcinomaHu Wang0Yilong Gao1Fengran Guo2Pengfei Zhou3Ziyang Ma4Kui Chi5Jiaqing Ye6Hao Sun7Xingyu He8Bei Shi9Yaxuan Wang10Zhenwei Han11Department of Urology, The First Hospital of Jiaxing & The Affiliated Hospital of Jiaxing University, Jiaxing 314033, China; Department of Urology, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, ChinaDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, ChinaDepartment of Urology, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, ChinaZhengding County People's Hospital, Shijiazhuang, ChinaDepartment of Urology, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, ChinaDepartment of Vascular surgery, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, ChinaDepartment of Clinical laboratory, the Third Hospital of Hebei Medical University, Shijiazhuang 050000, ChinaDepartment of Urology, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, ChinaDepartment of Pathology, Hebei Medical University, Shijiazhuang, China; Center of Metabolic Diseases and Cancer Research, Institute of Medical and Health Science of Hebei Medical University, Shijiazhuang, ChinaDepartment of Urology, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, ChinaDepartment of Urology, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China; Co-Corresponding author.Department of Urology, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China; Corresponding author.Background: Our previous studies have shown that estrogen receptor beta (ERβ) can promote the progression of clear cell renal cell carcinoma (ccRCC) by downregulating the expression of circATP2B1 and miR-204–3p. Here, we found that ERβ might promote the epithelial-mesenchymal transition(EMT) of ccRCC by modulating the circATP2B1/miR-204–3p/TWIST1(Twist family basic helix-loop-helix transcription factor 1) signaling pathway. Methods: We utilized bioinformatics analysis to determine the clinical significance of TWIST1 in ccRCC. The expression of TWIST1 in ccRCC tissues and cells was examined using immunohistochemistry, real-time quantitative polymerase chain reaction and western blotting assay. Chromatin Immunoprecipitation assay were conducted to validate the relationship between ERβ and TWIST1. Luciferase reporter gene assays were employed to validate the binding targets of TWIST1 and miR-204–3p. The role of TWIST1 in ccRCC was studied through in vitro and in vivo experiments. Transwell assays and wound healing assays were used to assess the impact of TWIST1 on the invasive and migratory abilities of ccRCC cells. Results: Mechanism analysis revealed that miR-204–3p can inhibit TWIST1 by targeting its 3′ untranslated region. Additionally, TWIST1 can promote ERβ transcription by directly binding to transcription factor binding site in the ERβ promoter region, forming a positive feedback loop. These in vitro data were further validated in an in vivo mouse model. Importantly, analysis of data from the TCGA-KIRC database further confirmed the above in vitro/in vivo findings. Conclusions: Together, our results suggest that ERβ/circATP2B1/miR-204–3p/TWIST1 can promote EMT by forming a positive feedback loop, thus promoting the progression of ccRCC. Targeting this newly identified signaling pathway may more effectively control the progression of ccRCC.http://www.sciencedirect.com/science/article/pii/S1936523324003401estrogen receptor betaccRCCcircATP2B1TWIST1EMT |
| spellingShingle | Hu Wang Yilong Gao Fengran Guo Pengfei Zhou Ziyang Ma Kui Chi Jiaqing Ye Hao Sun Xingyu He Bei Shi Yaxuan Wang Zhenwei Han ERβ-regulated circATP2B1/miR-204–3p/TWIST1 positive feedback loop facilitates epithelial to mesenchymal transition in clear cell renal cell carcinoma Translational Oncology estrogen receptor beta ccRCC circATP2B1 TWIST1 EMT |
| title | ERβ-regulated circATP2B1/miR-204–3p/TWIST1 positive feedback loop facilitates epithelial to mesenchymal transition in clear cell renal cell carcinoma |
| title_full | ERβ-regulated circATP2B1/miR-204–3p/TWIST1 positive feedback loop facilitates epithelial to mesenchymal transition in clear cell renal cell carcinoma |
| title_fullStr | ERβ-regulated circATP2B1/miR-204–3p/TWIST1 positive feedback loop facilitates epithelial to mesenchymal transition in clear cell renal cell carcinoma |
| title_full_unstemmed | ERβ-regulated circATP2B1/miR-204–3p/TWIST1 positive feedback loop facilitates epithelial to mesenchymal transition in clear cell renal cell carcinoma |
| title_short | ERβ-regulated circATP2B1/miR-204–3p/TWIST1 positive feedback loop facilitates epithelial to mesenchymal transition in clear cell renal cell carcinoma |
| title_sort | erβ regulated circatp2b1 mir 204 3p twist1 positive feedback loop facilitates epithelial to mesenchymal transition in clear cell renal cell carcinoma |
| topic | estrogen receptor beta ccRCC circATP2B1 TWIST1 EMT |
| url | http://www.sciencedirect.com/science/article/pii/S1936523324003401 |
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