PTOV1‐AS1 desensitizes colorectal cancer cells to 5‐FU through depressing miR‐149‐5p to activate the positive feedback loop with Wnt/β‐catenin pathway
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| Main Authors: | , , , , , , , , , |
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| Format: | Artículo Open Access |
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Wiley
2024
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| _version_ | 1867019622169968640 |
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| author | Yanan Chen Xiaobei Mao Yichen Xu Lin Li Jian Geng Tingting Dai Qian Wang Lijun Xue Leilei Tao Xiaobei Liu |
| author_facet | Yanan Chen Xiaobei Mao Yichen Xu Lin Li Jian Geng Tingting Dai Qian Wang Lijun Xue Leilei Tao Xiaobei Liu Yanan Chen Xiaobei Mao Yichen Xu Lin Li Jian Geng Tingting Dai Qian Wang Lijun Xue Leilei Tao Xiaobei Liu |
| collection | Wiley Open Access |
| contents | PTOV1‐AS1 desensitizes colorectal cancer cells to 5‐FU through depressing miR‐149‐5p to activate the positive feedback loop with Wnt/β‐catenin pathway Yanan Chen Xiaobei Mao Yichen Xu Lin Li Jian Geng Tingting Dai Qian Wang Lijun Xue Leilei Tao Xiaobei Liu Phytotherapy Research Abstract5‐Fluorouracil is a commonly used chemotherapy drug for colorectal cancer. Resistance to 5‐Fluorouracil remains a challenge. This research aimed to explore the mechanism of 5‐Fluorouracil resistance in colorectal cancer. RT‐qPCR and Western blot were used to determine the RNA and protein expression in both cells and exosome. Assays in vitro and in vivo were performed to measure the role of miR‐149‐5p in colorectal cancer cells. RIP, luciferase activity report, and RNA pulldown assay were applied to detect the association of PTOV1‐AS1, SUV39H1, miR‐149‐5p, and FOXM1. MiR‐149‐5p was down‐expressed in 5‐Fluorouracil‐resistant cells. MiR‐149‐5p enhanced the effectiveness of 5‐Fluorouracil both in vitro and in vivo. Sensitive colorectal cancer cells released exosomal miR‐149‐5p to sensitize resistant cells to chemotherapy. Mechanistically, miR‐149‐5p targeted the FOXM1 to inactivate Wnt/β‐catenin pathway, and PTOV1‐AS1 recruited SUV39H1 to suppress miR‐149‐5p transcription, in turn activating Wnt/β‐catenin pathway, and forming a positive feedback loop with FOXM1. PTOV1‐AS1 inhibits miR‐149‐5p by a positive feedback loop with FOXM1‐mediated Wnt/β‐catenin pathway, which provides insights into a potential novel target for enhancing the effectiveness of chemotherapy in colorectal cancer patients. 10.1002/ptr.8095 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1002/ptr.8095 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_ptr_8095 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2024 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | PTOV1‐AS1 desensitizes colorectal cancer cells to 5‐FU through depressing miR‐149‐5p to activate the positive feedback loop with Wnt/β‐catenin pathway Yanan Chen Xiaobei Mao Yichen Xu Lin Li Jian Geng Tingting Dai Qian Wang Lijun Xue Leilei Tao Xiaobei Liu Phytotherapy Research PTOV1‐AS1 desensitizes colorectal cancer cells to 5‐FU through depressing miR‐149‐5p to activate the positive feedback loop with Wnt/β‐catenin pathway Yanan Chen Xiaobei Mao Yichen Xu Lin Li Jian Geng Tingting Dai Qian Wang Lijun Xue Leilei Tao Xiaobei Liu Phytotherapy Research Abstract5‐Fluorouracil is a commonly used chemotherapy drug for colorectal cancer. Resistance to 5‐Fluorouracil remains a challenge. This research aimed to explore the mechanism of 5‐Fluorouracil resistance in colorectal cancer. RT‐qPCR and Western blot were used to determine the RNA and protein expression in both cells and exosome. Assays in vitro and in vivo were performed to measure the role of miR‐149‐5p in colorectal cancer cells. RIP, luciferase activity report, and RNA pulldown assay were applied to detect the association of PTOV1‐AS1, SUV39H1, miR‐149‐5p, and FOXM1. MiR‐149‐5p was down‐expressed in 5‐Fluorouracil‐resistant cells. MiR‐149‐5p enhanced the effectiveness of 5‐Fluorouracil both in vitro and in vivo. Sensitive colorectal cancer cells released exosomal miR‐149‐5p to sensitize resistant cells to chemotherapy. Mechanistically, miR‐149‐5p targeted the FOXM1 to inactivate Wnt/β‐catenin pathway, and PTOV1‐AS1 recruited SUV39H1 to suppress miR‐149‐5p transcription, in turn activating Wnt/β‐catenin pathway, and forming a positive feedback loop with FOXM1. PTOV1‐AS1 inhibits miR‐149‐5p by a positive feedback loop with FOXM1‐mediated Wnt/β‐catenin pathway, which provides insights into a potential novel target for enhancing the effectiveness of chemotherapy in colorectal cancer patients. 10.1002/ptr.8095 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | PTOV1‐AS1 desensitizes colorectal cancer cells to 5‐FU through depressing miR‐149‐5p to activate the positive feedback loop with Wnt/β‐catenin pathway |
| topic | Phytotherapy Research |
| url | https://onlinelibrary.wiley.com/doi/10.1002/ptr.8095 |