CircSATB1 Promotes Colorectal Cancer Liver Metastasis through Facilitating FKBP8 Degradation via RNF25‐Mediated Ubiquitination
Abstract Colorectal cancer (CRC) is one of the most common cancers worldwide and liver metastasis is the leading reason for its mortality. Circular RNAs (circRNAs) are conclusively associated with the progression of various cancers, rendering the exploration of its specific mechanisms in colorectal...
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| Format: | Article |
| Language: | English |
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Wiley
2025-04-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202406962 |
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| author | Chuan Zhang Chuanxin Tian Renzhong Zhu Chen Chen Chi Jin Xiaowei Wang Lejia Sun Wen Peng Dongjian Ji Yue Zhang Yueming Sun |
| author_facet | Chuan Zhang Chuanxin Tian Renzhong Zhu Chen Chen Chi Jin Xiaowei Wang Lejia Sun Wen Peng Dongjian Ji Yue Zhang Yueming Sun |
| author_sort | Chuan Zhang |
| collection | DOAJ |
| description | Abstract Colorectal cancer (CRC) is one of the most common cancers worldwide and liver metastasis is the leading reason for its mortality. Circular RNAs (circRNAs) are conclusively associated with the progression of various cancers, rendering the exploration of its specific mechanisms in colorectal cancer liver metastasis(CRLM) highly valuable. Combined with GEO (Gene Expression Omnibus) databases and clinical data in our center, we found that high expression of circSATB1 is closely related to the progression of CRLM. Functionally, circSATB1 could significantly promote the metastatic ability of CRC cells in vitro and in vivo. Mechanistically, circSATB1 facilitated the RNF25‐mediated ubiquitylation and degradation of FKBP8, releasing its inhibitory effects on mTOR signaling. In this process, circSATB1 acted as a scaffold for RNF25‐FKBP8 complexes. Additionally, circSATB1 could be packaged in exosomes and secreted from the CRC primary tumors into plasma. In conclusion, this study uncovered a new circSATB1 that acts as a potent promoter of CRLM and offers novel insights into the precision therapeutic strategies for CRLM. |
| format | Article |
| id | doaj-art-c718d6a4cafb4458928bf932ba7e13f6 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-c718d6a4cafb4458928bf932ba7e13f62025-08-20T01:51:39ZengWileyAdvanced Science2198-38442025-04-011213n/an/a10.1002/advs.202406962CircSATB1 Promotes Colorectal Cancer Liver Metastasis through Facilitating FKBP8 Degradation via RNF25‐Mediated UbiquitinationChuan Zhang0Chuanxin Tian1Renzhong Zhu2Chen Chen3Chi Jin4Xiaowei Wang5Lejia Sun6Wen Peng7Dongjian Ji8Yue Zhang9Yueming Sun10Department of General SurgeryThe First Affiliated Hospital of Nanjing Medical UniversityColorectal Institute of Nanjing Medical UniversityNanjing210000ChinaDepartment of General SurgeryThe First Affiliated Hospital of Nanjing Medical UniversityColorectal Institute of Nanjing Medical UniversityNanjing210000ChinaInstitute of Translational Medicine, Medical CollegeYangzhou UniversityYangzhou225000ChinaDepartment of General SurgeryThe First Affiliated Hospital of Nanjing Medical UniversityColorectal Institute of Nanjing Medical UniversityNanjing210000ChinaDepartment of General SurgeryThe First Affiliated Hospital of Nanjing Medical UniversityColorectal Institute of Nanjing Medical UniversityNanjing210000ChinaDepartment of General SurgeryThe First Affiliated Hospital of Nanjing Medical UniversityColorectal Institute of Nanjing Medical UniversityNanjing210000ChinaDepartment of General SurgeryThe First Affiliated Hospital of Nanjing Medical UniversityColorectal Institute of Nanjing Medical UniversityNanjing210000ChinaDepartment of General SurgeryThe First Affiliated Hospital of Nanjing Medical UniversityColorectal Institute of Nanjing Medical UniversityNanjing210000ChinaDepartment of General SurgeryThe First Affiliated Hospital of Nanjing Medical UniversityColorectal Institute of Nanjing Medical UniversityNanjing210000ChinaDepartment of General SurgeryThe First Affiliated Hospital of Nanjing Medical UniversityColorectal Institute of Nanjing Medical UniversityNanjing210000ChinaDepartment of General SurgeryThe First Affiliated Hospital of Nanjing Medical UniversityColorectal Institute of Nanjing Medical UniversityNanjing210000ChinaAbstract Colorectal cancer (CRC) is one of the most common cancers worldwide and liver metastasis is the leading reason for its mortality. Circular RNAs (circRNAs) are conclusively associated with the progression of various cancers, rendering the exploration of its specific mechanisms in colorectal cancer liver metastasis(CRLM) highly valuable. Combined with GEO (Gene Expression Omnibus) databases and clinical data in our center, we found that high expression of circSATB1 is closely related to the progression of CRLM. Functionally, circSATB1 could significantly promote the metastatic ability of CRC cells in vitro and in vivo. Mechanistically, circSATB1 facilitated the RNF25‐mediated ubiquitylation and degradation of FKBP8, releasing its inhibitory effects on mTOR signaling. In this process, circSATB1 acted as a scaffold for RNF25‐FKBP8 complexes. Additionally, circSATB1 could be packaged in exosomes and secreted from the CRC primary tumors into plasma. In conclusion, this study uncovered a new circSATB1 that acts as a potent promoter of CRLM and offers novel insights into the precision therapeutic strategies for CRLM.https://doi.org/10.1002/advs.202406962circSATB1colorectal cancerFKBP8liver metastasisRNF25 |
| spellingShingle | Chuan Zhang Chuanxin Tian Renzhong Zhu Chen Chen Chi Jin Xiaowei Wang Lejia Sun Wen Peng Dongjian Ji Yue Zhang Yueming Sun CircSATB1 Promotes Colorectal Cancer Liver Metastasis through Facilitating FKBP8 Degradation via RNF25‐Mediated Ubiquitination Advanced Science circSATB1 colorectal cancer FKBP8 liver metastasis RNF25 |
| title | CircSATB1 Promotes Colorectal Cancer Liver Metastasis through Facilitating FKBP8 Degradation via RNF25‐Mediated Ubiquitination |
| title_full | CircSATB1 Promotes Colorectal Cancer Liver Metastasis through Facilitating FKBP8 Degradation via RNF25‐Mediated Ubiquitination |
| title_fullStr | CircSATB1 Promotes Colorectal Cancer Liver Metastasis through Facilitating FKBP8 Degradation via RNF25‐Mediated Ubiquitination |
| title_full_unstemmed | CircSATB1 Promotes Colorectal Cancer Liver Metastasis through Facilitating FKBP8 Degradation via RNF25‐Mediated Ubiquitination |
| title_short | CircSATB1 Promotes Colorectal Cancer Liver Metastasis through Facilitating FKBP8 Degradation via RNF25‐Mediated Ubiquitination |
| title_sort | circsatb1 promotes colorectal cancer liver metastasis through facilitating fkbp8 degradation via rnf25 mediated ubiquitination |
| topic | circSATB1 colorectal cancer FKBP8 liver metastasis RNF25 |
| url | https://doi.org/10.1002/advs.202406962 |
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