Multi-omics reveals that ST6GAL1 promotes colorectal cancer progression through LGALS3BP sialylation
ST6 β-galactoside α2,6-sialyltransferase 1 (ST6GAL1), a crucial enzyme for tumor-associated sialic acid modification, has been reported to positively correlate with colorectal cancer (CRC) tumorigenesis; however, the underlying mechanism remains unclear. To elucidate the protumor mechanisms of ST6G...
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Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina
2025-02-01
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| Series: | Biomolecules & Biomedicine |
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| Online Access: | https://bjbms.org/ojs/index.php/bjbms/article/view/11663 |
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| author | Yuanchao Shi Zhenzhong Pan Jingwei Duan Zexing Wang Yiliang Fang Bo Tang Quanlin Guan |
| author_facet | Yuanchao Shi Zhenzhong Pan Jingwei Duan Zexing Wang Yiliang Fang Bo Tang Quanlin Guan |
| author_sort | Yuanchao Shi |
| collection | DOAJ |
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ST6 β-galactoside α2,6-sialyltransferase 1 (ST6GAL1), a crucial enzyme for tumor-associated sialic acid modification, has been reported to positively correlate with colorectal cancer (CRC) tumorigenesis; however, the underlying mechanism remains unclear. To elucidate the protumor mechanisms of ST6GAL1, we performed transcriptomic and N-glycoproteomic analyses and in vitro assays. We found that ST6GAL1 was significantly upregulated in tumor samples than in matched normal samples by analyzing fresh clinical samples from public databases (mean mRNA expression level: tumor vs. normal samples = 0.002712:0.000966, P < 0.05, n = 22). The in vitro results revealed that ST6GAL1 overexpression promoted CRC cell proliferation, migration, and chemoresistance, which were significantly blocked by its knockdown. Transcriptomic data showed that many genes related to the four modules (proliferation/cell cycle, migration, motility, and epithelial-mesenchymal transition) were upregulated after ST6GAL1 overexpression but downregulated after ST6GAL1 knockdown. Furthermore, the N-glycoproteome data revealed that 25 substrates that were sialylated upon ST6GAL1 overexpression were related to protumor activity. Importantly, we found that knockdown of lectin galactoside-binding soluble 3-binding protein (LGALS3BP), a newly identified secreted substrate of ST6GAL1, significantly blocked the proliferation, invasion, and chemoresistance of CRC cells induced by ST6GAL1 overexpression. Treatment with sialidases (neuraminidases, NAs) also blocked the protumor activity of ST6GAL1. Thus, ST6GAL1-induced increased sialylation of substrates such as LGALS3BP and upregulation of protumor genes promote CRC tumorigenesis and chemoresistance, which provides important perspectives and new targets for the treatment of CRC.
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| format | Article |
| id | doaj-art-e366fd1ec2c1401383f2937e520b5c4e |
| institution | Kabale University |
| issn | 2831-0896 2831-090X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina |
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| series | Biomolecules & Biomedicine |
| spelling | doaj-art-e366fd1ec2c1401383f2937e520b5c4e2025-02-08T16:42:39ZengAssociation of Basic Medical Sciences of Federation of Bosnia and HerzegovinaBiomolecules & Biomedicine2831-08962831-090X2025-02-0110.17305/bb.2025.11663Multi-omics reveals that ST6GAL1 promotes colorectal cancer progression through LGALS3BP sialylationYuanchao Shi0Zhenzhong Pan1Jingwei Duan2Zexing Wang3Yiliang Fang4Bo Tang5Quanlin Guan6The First Clinical Academy of Lanzhou University, Lanzhou University, Lanzhou, China; Department of General Surgery and Gastrointestinal Oncology Surgery, Lanzhou University First Hospital, Lanzhou, ChinaState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, ChinaEmergency department, Peking University Third Hospital, Beijing, ChinaSchool of Medicine, Chongqing University, Chongqing, ChinaDepartment of Neurology, Army Medical University Xinqiao Hospital, Chongqing, ChinaDepartment of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Third Military Medical University Southwest Hospital, Chongqing, ChinaThe First Clinical Academy of Lanzhou University, Lanzhou University, Lanzhou, China; Department of General Surgery and Gastrointestinal Oncology Surgery, Lanzhou University First Hospital, Lanzhou, China ST6 β-galactoside α2,6-sialyltransferase 1 (ST6GAL1), a crucial enzyme for tumor-associated sialic acid modification, has been reported to positively correlate with colorectal cancer (CRC) tumorigenesis; however, the underlying mechanism remains unclear. To elucidate the protumor mechanisms of ST6GAL1, we performed transcriptomic and N-glycoproteomic analyses and in vitro assays. We found that ST6GAL1 was significantly upregulated in tumor samples than in matched normal samples by analyzing fresh clinical samples from public databases (mean mRNA expression level: tumor vs. normal samples = 0.002712:0.000966, P < 0.05, n = 22). The in vitro results revealed that ST6GAL1 overexpression promoted CRC cell proliferation, migration, and chemoresistance, which were significantly blocked by its knockdown. Transcriptomic data showed that many genes related to the four modules (proliferation/cell cycle, migration, motility, and epithelial-mesenchymal transition) were upregulated after ST6GAL1 overexpression but downregulated after ST6GAL1 knockdown. Furthermore, the N-glycoproteome data revealed that 25 substrates that were sialylated upon ST6GAL1 overexpression were related to protumor activity. Importantly, we found that knockdown of lectin galactoside-binding soluble 3-binding protein (LGALS3BP), a newly identified secreted substrate of ST6GAL1, significantly blocked the proliferation, invasion, and chemoresistance of CRC cells induced by ST6GAL1 overexpression. Treatment with sialidases (neuraminidases, NAs) also blocked the protumor activity of ST6GAL1. Thus, ST6GAL1-induced increased sialylation of substrates such as LGALS3BP and upregulation of protumor genes promote CRC tumorigenesis and chemoresistance, which provides important perspectives and new targets for the treatment of CRC. https://bjbms.org/ojs/index.php/bjbms/article/view/11663Colorectal cancerCRCST6 β-galactoside α2,6-sialyltransferaseST6GAL1lectin galactoside-binding soluble 3-binding proteinLGALS3BP |
| spellingShingle | Yuanchao Shi Zhenzhong Pan Jingwei Duan Zexing Wang Yiliang Fang Bo Tang Quanlin Guan Multi-omics reveals that ST6GAL1 promotes colorectal cancer progression through LGALS3BP sialylation Biomolecules & Biomedicine Colorectal cancer CRC ST6 β-galactoside α2,6-sialyltransferase ST6GAL1 lectin galactoside-binding soluble 3-binding protein LGALS3BP |
| title | Multi-omics reveals that ST6GAL1 promotes colorectal cancer progression through LGALS3BP sialylation |
| title_full | Multi-omics reveals that ST6GAL1 promotes colorectal cancer progression through LGALS3BP sialylation |
| title_fullStr | Multi-omics reveals that ST6GAL1 promotes colorectal cancer progression through LGALS3BP sialylation |
| title_full_unstemmed | Multi-omics reveals that ST6GAL1 promotes colorectal cancer progression through LGALS3BP sialylation |
| title_short | Multi-omics reveals that ST6GAL1 promotes colorectal cancer progression through LGALS3BP sialylation |
| title_sort | multi omics reveals that st6gal1 promotes colorectal cancer progression through lgals3bp sialylation |
| topic | Colorectal cancer CRC ST6 β-galactoside α2,6-sialyltransferase ST6GAL1 lectin galactoside-binding soluble 3-binding protein LGALS3BP |
| url | https://bjbms.org/ojs/index.php/bjbms/article/view/11663 |
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