WYC-209 inhibited GC malignant progression by down-regulating WNT4 through RARα
Gastric cancer (GC) has been a major health burden all over the world but there are fewer promising chemotherapeutic drugs due to its multidrug resistance. It has been reported that WYC-209 suppresses the growth and metastasis of tumor-repopulating cells but the effect on GC was not explored. MTT, c...
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Taylor & Francis Group
2024-12-01
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| Series: | Cancer Biology & Therapy |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/15384047.2023.2299288 |
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| author | Zhenyuan Qian Wenfa Lin Xufan Cai Jianzhang Wu Kun Ke Zaiyuan Ye Fang Wu |
| author_facet | Zhenyuan Qian Wenfa Lin Xufan Cai Jianzhang Wu Kun Ke Zaiyuan Ye Fang Wu |
| author_sort | Zhenyuan Qian |
| collection | DOAJ |
| description | Gastric cancer (GC) has been a major health burden all over the world but there are fewer promising chemotherapeutic drugs due to its multidrug resistance. It has been reported that WYC-209 suppresses the growth and metastasis of tumor-repopulating cells but the effect on GC was not explored. MTT, colony formation, and transwell assays were performed to examine the effects of WYC-209 on the proliferation, colony growth, and mobility of GC cells. Western blotting and qRT-PCR were used to detect the expression of proteins and mRNA. RNA-seq and enrichment analyses were conducted for the differentially expressed genes and enriched biological processes and pathways. The rescue experiments were carried out for further validation. Besides, we constructed xenograft model to confirm the effect of WYC-209 in vivo. The dual-luciferase reporter and Chromatin immunoprecipitation were implemented to confirm the underlying mechanism. WYC-209 exerted excellent anti-cancer effects both in vitro and in vivo. Based on RNA-seq and enrichment analyses, we found that Wnt family member 4 (WNT4) was significantly down-regulated. More importantly, WNT4 overexpression breached the inhibitory effect of WYC-209 on GC progression. Mechanically, WYC-209 significantly promoted the binding between retinoic acid receptor α (RARα) and WNT4 promoter. WYC-209 exerts anti-tumor effects in GC by down-regulating the expression of WNT4 via RARα. |
| format | Article |
| id | doaj-art-4b8db1fd643e4227b4a433c96b0faad1 |
| institution | OA Journals |
| issn | 1538-4047 1555-8576 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Cancer Biology & Therapy |
| spelling | doaj-art-4b8db1fd643e4227b4a433c96b0faad12025-08-20T02:38:14ZengTaylor & Francis GroupCancer Biology & Therapy1538-40471555-85762024-12-0125110.1080/15384047.2023.2299288WYC-209 inhibited GC malignant progression by down-regulating WNT4 through RARαZhenyuan Qian0Wenfa Lin1Xufan Cai2Jianzhang Wu3Kun Ke4Zaiyuan Ye5Fang Wu6General Surgery, Cancer Center, Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, ChinaSchool of Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaSchool of Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaGeneral Surgery, Cancer Center, Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, ChinaGeneral Surgery, Cancer Center, Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, ChinaGeneral Surgery, Cancer Center, Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, ChinaGeneral Surgery, Cancer Center, Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, ChinaGastric cancer (GC) has been a major health burden all over the world but there are fewer promising chemotherapeutic drugs due to its multidrug resistance. It has been reported that WYC-209 suppresses the growth and metastasis of tumor-repopulating cells but the effect on GC was not explored. MTT, colony formation, and transwell assays were performed to examine the effects of WYC-209 on the proliferation, colony growth, and mobility of GC cells. Western blotting and qRT-PCR were used to detect the expression of proteins and mRNA. RNA-seq and enrichment analyses were conducted for the differentially expressed genes and enriched biological processes and pathways. The rescue experiments were carried out for further validation. Besides, we constructed xenograft model to confirm the effect of WYC-209 in vivo. The dual-luciferase reporter and Chromatin immunoprecipitation were implemented to confirm the underlying mechanism. WYC-209 exerted excellent anti-cancer effects both in vitro and in vivo. Based on RNA-seq and enrichment analyses, we found that Wnt family member 4 (WNT4) was significantly down-regulated. More importantly, WNT4 overexpression breached the inhibitory effect of WYC-209 on GC progression. Mechanically, WYC-209 significantly promoted the binding between retinoic acid receptor α (RARα) and WNT4 promoter. WYC-209 exerts anti-tumor effects in GC by down-regulating the expression of WNT4 via RARα.https://www.tandfonline.com/doi/10.1080/15384047.2023.2299288GCWYC-209synthetic retinoidWNT4RARα |
| spellingShingle | Zhenyuan Qian Wenfa Lin Xufan Cai Jianzhang Wu Kun Ke Zaiyuan Ye Fang Wu WYC-209 inhibited GC malignant progression by down-regulating WNT4 through RARα Cancer Biology & Therapy GC WYC-209 synthetic retinoid WNT4 RARα |
| title | WYC-209 inhibited GC malignant progression by down-regulating WNT4 through RARα |
| title_full | WYC-209 inhibited GC malignant progression by down-regulating WNT4 through RARα |
| title_fullStr | WYC-209 inhibited GC malignant progression by down-regulating WNT4 through RARα |
| title_full_unstemmed | WYC-209 inhibited GC malignant progression by down-regulating WNT4 through RARα |
| title_short | WYC-209 inhibited GC malignant progression by down-regulating WNT4 through RARα |
| title_sort | wyc 209 inhibited gc malignant progression by down regulating wnt4 through rarα |
| topic | GC WYC-209 synthetic retinoid WNT4 RARα |
| url | https://www.tandfonline.com/doi/10.1080/15384047.2023.2299288 |
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