m6A-induced DEAD-box RNA helicase 21 enhances lipid metabolism via 3‑hydroxy-3-methylglutaryl-CoA synthases 1 in colorectal cancer
Background: Altered lipid metabolism is a well-known hallmark of cancer. However, the underlying mechanisms of altered lipid metabolism in colorectal cancer (CRC) progression requires further investigation. Previously we have revealed that DEAD-box RNA helicase 21 (DDX21) promotes CRC metastasis via...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-05-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523325001044 |
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| author | Huabin Gao Shuai Zheng Jiangtao Liang Yuting Wang Lin Chen Hui Li Yongyu Chen Fenfen Zhang Huijuan Shi Anjia Han |
| author_facet | Huabin Gao Shuai Zheng Jiangtao Liang Yuting Wang Lin Chen Hui Li Yongyu Chen Fenfen Zhang Huijuan Shi Anjia Han |
| author_sort | Huabin Gao |
| collection | DOAJ |
| description | Background: Altered lipid metabolism is a well-known hallmark of cancer. However, the underlying mechanisms of altered lipid metabolism in colorectal cancer (CRC) progression requires further investigation. Previously we have revealed that DEAD-box RNA helicase 21 (DDX21) promotes CRC metastasis via liquid-liquid phase separation. In this study, we identify DDX21 as a novel regulator of lipid metabolism in CRC. Methods: In vitro and in vivo assays illustrated the biological role of DDX21 and YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) in CRC lipid metabolism and progression. Bioinformatics analysis, ChIP, meRIP, RIP, RNA stability assay and dual-luciferase reporter assay were applied to explore the underlying molecular mechanisms. The expression levels and prognostic role of YTHDF1/DDX21/HMGCS1 axis in CRC patients were analyzed by immunohistochemical staining and Kaplan-Meier plotter. Results: DDX21 enhanced CRC progression via promoting lipid metabolism. Mechanistically, YTHDF1 enhanced DDX21 mRNA stability by recognizing its m6A-modified sites. DDX21 further binded to 3‑hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) promoter region and directly activated HMGCS1 transcription. Moreover, our clinical data showed that a simultaneously high expression of YTHDF1, DDX21 and HMGCS1 predicted an unfavorable overall survival in CRC patients. Conclusions: Our study demonstrates that the YTHDF1/DDX21/HMGCS1 axis promotes CRC progression via regulating lipid metabolism and DDX21 might be a promising target for CRC therapy. |
| format | Article |
| id | doaj-art-09bc6ff65e9e4b1ab2b0eba73e98bf33 |
| institution | DOAJ |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-09bc6ff65e9e4b1ab2b0eba73e98bf332025-08-20T03:03:27ZengElsevierTranslational Oncology1936-52332025-05-015510237310.1016/j.tranon.2025.102373m6A-induced DEAD-box RNA helicase 21 enhances lipid metabolism via 3‑hydroxy-3-methylglutaryl-CoA synthases 1 in colorectal cancerHuabin Gao0Shuai Zheng1Jiangtao Liang2Yuting Wang3Lin Chen4Hui Li5Yongyu Chen6Fenfen Zhang7Huijuan Shi8Anjia Han9Department of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, ChinaDepartment of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, ChinaDepartment of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, ChinaDepartment of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, ChinaDepartment of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, ChinaDepartment of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, ChinaDepartment of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, ChinaDepartment of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, ChinaCorresponding authors at: Department of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, 58, Zhongshan Road II, Guangzhou 510080, China.; Department of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, ChinaCorresponding authors at: Department of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, 58, Zhongshan Road II, Guangzhou 510080, China.; Department of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, ChinaBackground: Altered lipid metabolism is a well-known hallmark of cancer. However, the underlying mechanisms of altered lipid metabolism in colorectal cancer (CRC) progression requires further investigation. Previously we have revealed that DEAD-box RNA helicase 21 (DDX21) promotes CRC metastasis via liquid-liquid phase separation. In this study, we identify DDX21 as a novel regulator of lipid metabolism in CRC. Methods: In vitro and in vivo assays illustrated the biological role of DDX21 and YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) in CRC lipid metabolism and progression. Bioinformatics analysis, ChIP, meRIP, RIP, RNA stability assay and dual-luciferase reporter assay were applied to explore the underlying molecular mechanisms. The expression levels and prognostic role of YTHDF1/DDX21/HMGCS1 axis in CRC patients were analyzed by immunohistochemical staining and Kaplan-Meier plotter. Results: DDX21 enhanced CRC progression via promoting lipid metabolism. Mechanistically, YTHDF1 enhanced DDX21 mRNA stability by recognizing its m6A-modified sites. DDX21 further binded to 3‑hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) promoter region and directly activated HMGCS1 transcription. Moreover, our clinical data showed that a simultaneously high expression of YTHDF1, DDX21 and HMGCS1 predicted an unfavorable overall survival in CRC patients. Conclusions: Our study demonstrates that the YTHDF1/DDX21/HMGCS1 axis promotes CRC progression via regulating lipid metabolism and DDX21 might be a promising target for CRC therapy.http://www.sciencedirect.com/science/article/pii/S1936523325001044DDX21Colorectal cancerLipid metabolism |
| spellingShingle | Huabin Gao Shuai Zheng Jiangtao Liang Yuting Wang Lin Chen Hui Li Yongyu Chen Fenfen Zhang Huijuan Shi Anjia Han m6A-induced DEAD-box RNA helicase 21 enhances lipid metabolism via 3‑hydroxy-3-methylglutaryl-CoA synthases 1 in colorectal cancer Translational Oncology DDX21 Colorectal cancer Lipid metabolism |
| title | m6A-induced DEAD-box RNA helicase 21 enhances lipid metabolism via 3‑hydroxy-3-methylglutaryl-CoA synthases 1 in colorectal cancer |
| title_full | m6A-induced DEAD-box RNA helicase 21 enhances lipid metabolism via 3‑hydroxy-3-methylglutaryl-CoA synthases 1 in colorectal cancer |
| title_fullStr | m6A-induced DEAD-box RNA helicase 21 enhances lipid metabolism via 3‑hydroxy-3-methylglutaryl-CoA synthases 1 in colorectal cancer |
| title_full_unstemmed | m6A-induced DEAD-box RNA helicase 21 enhances lipid metabolism via 3‑hydroxy-3-methylglutaryl-CoA synthases 1 in colorectal cancer |
| title_short | m6A-induced DEAD-box RNA helicase 21 enhances lipid metabolism via 3‑hydroxy-3-methylglutaryl-CoA synthases 1 in colorectal cancer |
| title_sort | m6a induced dead box rna helicase 21 enhances lipid metabolism via 3 hydroxy 3 methylglutaryl coa synthases 1 in colorectal cancer |
| topic | DDX21 Colorectal cancer Lipid metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S1936523325001044 |
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