DDX17 induces epithelial-mesenchymal transition and metastasis through the miR-149-3p/CYBRD1 pathway in colorectal cancer
Abstract DEAD box helicase 17 (DDX17) has been reported to be involved in the initiation and development of several cancers. However, the functional role and mechanisms of DDX17 in colorectal cancer (CRC) malignant progression and metastasis remain unclear. Here, we reported that DDX17 expression wa...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-01-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-05508-y |
| _version_ | 1797958494968610816 |
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| author | Gang Zhao Qijing Wang Yue Zhang Rui Gu Min Liu Qin Li Jie Zhang Hang Yuan Tianyu Feng Deqiong Ou Siqi Li Shan Li Kai Li Chunfen Mo Ping Lin |
| author_facet | Gang Zhao Qijing Wang Yue Zhang Rui Gu Min Liu Qin Li Jie Zhang Hang Yuan Tianyu Feng Deqiong Ou Siqi Li Shan Li Kai Li Chunfen Mo Ping Lin |
| author_sort | Gang Zhao |
| collection | DOAJ |
| description | Abstract DEAD box helicase 17 (DDX17) has been reported to be involved in the initiation and development of several cancers. However, the functional role and mechanisms of DDX17 in colorectal cancer (CRC) malignant progression and metastasis remain unclear. Here, we reported that DDX17 expression was increased in CRC tissues compared with noncancerous mucosa tissues and further upregulated in CRC liver metastasis compared with patient-paired primary tumors. High levels of DDX17 were significantly correlated with aggressive phenotypes and worse clinical outcomes in CRC patients. Ectopic expression of DDX17 promoted cell migration and invasion in vitro and in vivo, while the opposite results were obtained in DDX17-deficient CRC cells. We identified miR-149-3p as a potential downstream miRNA of DDX17 through RNA sequencing analysis, and miR-149-3p displayed a suppressive effect on the metastatic potential of CRC cells. We demonstrated that CYBRD1 (a ferric reductase that contributes to dietary iron absorption) was a direct target of miR-149-3p and that miR-149-3p was required for DDX17-mediated regulation of CYBRD1 expression. Moreover, DDX17 contributed to the metastasis and epithelial to mesenchymal transition (EMT) of CRC cells via downregulation of miR-149-3p, which resulted in increased CYBRD1 expression. In conclusion, our findings not only highlight the significance of DDX17 in the aggressive development and prognosis of CRC patients, but also reveal a novel mechanism underlying DDX17-mediated CRC cell metastasis and EMT progression through manipulation of the miR-149-3p/CYBRD1 pathway. |
| first_indexed | 2024-04-11T00:19:54Z |
| format | Article |
| id | doaj.art-98ce5b2e75c84732b997373e6980a841 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-11T00:19:54Z |
| publishDate | 2023-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-98ce5b2e75c84732b997373e6980a8412023-01-08T12:22:13ZengNature Publishing GroupCell Death and Disease2041-48892023-01-0114111310.1038/s41419-022-05508-yDDX17 induces epithelial-mesenchymal transition and metastasis through the miR-149-3p/CYBRD1 pathway in colorectal cancerGang Zhao0Qijing Wang1Yue Zhang2Rui Gu3Min Liu4Qin Li5Jie Zhang6Hang Yuan7Tianyu Feng8Deqiong Ou9Siqi Li10Shan Li11Kai Li12Chunfen Mo13Ping Lin14Lab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan UniversityLab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan UniversityLab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan UniversityLab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan UniversityLab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan UniversityLab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan UniversityLab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan UniversityLab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan UniversityLab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan UniversityLab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan UniversityLab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan UniversityLab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan UniversityLab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan UniversityDepartment of General Surgery, Second Affiliated Hospital of Chengdu Medical College (China National Nuclear Corporation 416 Hospital)Lab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan UniversityAbstract DEAD box helicase 17 (DDX17) has been reported to be involved in the initiation and development of several cancers. However, the functional role and mechanisms of DDX17 in colorectal cancer (CRC) malignant progression and metastasis remain unclear. Here, we reported that DDX17 expression was increased in CRC tissues compared with noncancerous mucosa tissues and further upregulated in CRC liver metastasis compared with patient-paired primary tumors. High levels of DDX17 were significantly correlated with aggressive phenotypes and worse clinical outcomes in CRC patients. Ectopic expression of DDX17 promoted cell migration and invasion in vitro and in vivo, while the opposite results were obtained in DDX17-deficient CRC cells. We identified miR-149-3p as a potential downstream miRNA of DDX17 through RNA sequencing analysis, and miR-149-3p displayed a suppressive effect on the metastatic potential of CRC cells. We demonstrated that CYBRD1 (a ferric reductase that contributes to dietary iron absorption) was a direct target of miR-149-3p and that miR-149-3p was required for DDX17-mediated regulation of CYBRD1 expression. Moreover, DDX17 contributed to the metastasis and epithelial to mesenchymal transition (EMT) of CRC cells via downregulation of miR-149-3p, which resulted in increased CYBRD1 expression. In conclusion, our findings not only highlight the significance of DDX17 in the aggressive development and prognosis of CRC patients, but also reveal a novel mechanism underlying DDX17-mediated CRC cell metastasis and EMT progression through manipulation of the miR-149-3p/CYBRD1 pathway.https://doi.org/10.1038/s41419-022-05508-y |
| spellingShingle | Gang Zhao Qijing Wang Yue Zhang Rui Gu Min Liu Qin Li Jie Zhang Hang Yuan Tianyu Feng Deqiong Ou Siqi Li Shan Li Kai Li Chunfen Mo Ping Lin DDX17 induces epithelial-mesenchymal transition and metastasis through the miR-149-3p/CYBRD1 pathway in colorectal cancer Cell Death and Disease |
| title | DDX17 induces epithelial-mesenchymal transition and metastasis through the miR-149-3p/CYBRD1 pathway in colorectal cancer |
| title_full | DDX17 induces epithelial-mesenchymal transition and metastasis through the miR-149-3p/CYBRD1 pathway in colorectal cancer |
| title_fullStr | DDX17 induces epithelial-mesenchymal transition and metastasis through the miR-149-3p/CYBRD1 pathway in colorectal cancer |
| title_full_unstemmed | DDX17 induces epithelial-mesenchymal transition and metastasis through the miR-149-3p/CYBRD1 pathway in colorectal cancer |
| title_short | DDX17 induces epithelial-mesenchymal transition and metastasis through the miR-149-3p/CYBRD1 pathway in colorectal cancer |
| title_sort | ddx17 induces epithelial mesenchymal transition and metastasis through the mir 149 3p cybrd1 pathway in colorectal cancer |
| url | https://doi.org/10.1038/s41419-022-05508-y |
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