ATRA upregulates OTUD6B to recruit CD8+ T cells to suppress colorectal liver metastasis by stabilizing DDX5/STAT3/CXCL11 axis
Abstract OTU deubiquitinase 6B (OTUD6B) study in tumors is gradually increasing; however, studies on the role of OTUD6B in colorectal cancer (CRC) are rare. OTUD6B was overexpressed in some human CRC and liver metastasis samples. Although OTUD6B facilitated migration and invasion in CRC cells, it ex...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2025-07-01
|
| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07837-0 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849760984735940608 |
|---|---|
| author | Jinglei Li Kunpeng Huang Bing Yang Xia Hu Bosheng Mei Xiang Cheng Xin Zhong Chuyi Cao Zihan Chen Hui Wang Jinxiang Zhang |
| author_facet | Jinglei Li Kunpeng Huang Bing Yang Xia Hu Bosheng Mei Xiang Cheng Xin Zhong Chuyi Cao Zihan Chen Hui Wang Jinxiang Zhang |
| author_sort | Jinglei Li |
| collection | DOAJ |
| description | Abstract OTU deubiquitinase 6B (OTUD6B) study in tumors is gradually increasing; however, studies on the role of OTUD6B in colorectal cancer (CRC) are rare. OTUD6B was overexpressed in some human CRC and liver metastasis samples. Although OTUD6B facilitated migration and invasion in CRC cells, it exhibited opposite effects on liver metastasis in immunodeficient and immunocompetent mice. We demonstrated that Otud6b enhanced metastasis in nude mice, but it recruited more CD8+ T cell infiltration in colorectal liver metastasis (CRLM) mouse model of C57BL/6J to inhibit CRLM through upregulating Cxcl11. Furthermore, we demonstrated that OTUD6B deubiquitinated and stabilized DDX5. Ectopically expressed DDX5 facilitated transcription factor STAT3 activation by resolving the RNA G-quadruplex structure of STAT3, resulting in a higher level of CXCL11 transcription and an increase in tumor-infiltrating CD8+ T cells. All-trans retinoic acid inhibited CRLM by upregulating OTUD6B. |
| format | Article |
| id | doaj-art-a9fb06b5bf7943f9a4dd50c7a73cd991 |
| institution | DOAJ |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-a9fb06b5bf7943f9a4dd50c7a73cd9912025-08-20T03:06:10ZengNature Publishing GroupCell Death and Disease2041-48892025-07-0116111410.1038/s41419-025-07837-0ATRA upregulates OTUD6B to recruit CD8+ T cells to suppress colorectal liver metastasis by stabilizing DDX5/STAT3/CXCL11 axisJinglei Li0Kunpeng Huang1Bing Yang2Xia Hu3Bosheng Mei4Xiang Cheng5Xin Zhong6Chuyi Cao7Zihan Chen8Hui Wang9Jinxiang Zhang10Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Gastroenterology, Second Affiliated Hospital of Nanchang UniversityDepartment of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Medical Genetics, Basic School of Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Medical Genetics, Basic School of Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract OTU deubiquitinase 6B (OTUD6B) study in tumors is gradually increasing; however, studies on the role of OTUD6B in colorectal cancer (CRC) are rare. OTUD6B was overexpressed in some human CRC and liver metastasis samples. Although OTUD6B facilitated migration and invasion in CRC cells, it exhibited opposite effects on liver metastasis in immunodeficient and immunocompetent mice. We demonstrated that Otud6b enhanced metastasis in nude mice, but it recruited more CD8+ T cell infiltration in colorectal liver metastasis (CRLM) mouse model of C57BL/6J to inhibit CRLM through upregulating Cxcl11. Furthermore, we demonstrated that OTUD6B deubiquitinated and stabilized DDX5. Ectopically expressed DDX5 facilitated transcription factor STAT3 activation by resolving the RNA G-quadruplex structure of STAT3, resulting in a higher level of CXCL11 transcription and an increase in tumor-infiltrating CD8+ T cells. All-trans retinoic acid inhibited CRLM by upregulating OTUD6B.https://doi.org/10.1038/s41419-025-07837-0 |
| spellingShingle | Jinglei Li Kunpeng Huang Bing Yang Xia Hu Bosheng Mei Xiang Cheng Xin Zhong Chuyi Cao Zihan Chen Hui Wang Jinxiang Zhang ATRA upregulates OTUD6B to recruit CD8+ T cells to suppress colorectal liver metastasis by stabilizing DDX5/STAT3/CXCL11 axis Cell Death and Disease |
| title | ATRA upregulates OTUD6B to recruit CD8+ T cells to suppress colorectal liver metastasis by stabilizing DDX5/STAT3/CXCL11 axis |
| title_full | ATRA upregulates OTUD6B to recruit CD8+ T cells to suppress colorectal liver metastasis by stabilizing DDX5/STAT3/CXCL11 axis |
| title_fullStr | ATRA upregulates OTUD6B to recruit CD8+ T cells to suppress colorectal liver metastasis by stabilizing DDX5/STAT3/CXCL11 axis |
| title_full_unstemmed | ATRA upregulates OTUD6B to recruit CD8+ T cells to suppress colorectal liver metastasis by stabilizing DDX5/STAT3/CXCL11 axis |
| title_short | ATRA upregulates OTUD6B to recruit CD8+ T cells to suppress colorectal liver metastasis by stabilizing DDX5/STAT3/CXCL11 axis |
| title_sort | atra upregulates otud6b to recruit cd8 t cells to suppress colorectal liver metastasis by stabilizing ddx5 stat3 cxcl11 axis |
| url | https://doi.org/10.1038/s41419-025-07837-0 |
| work_keys_str_mv | AT jingleili atraupregulatesotud6btorecruitcd8tcellstosuppresscolorectallivermetastasisbystabilizingddx5stat3cxcl11axis AT kunpenghuang atraupregulatesotud6btorecruitcd8tcellstosuppresscolorectallivermetastasisbystabilizingddx5stat3cxcl11axis AT bingyang atraupregulatesotud6btorecruitcd8tcellstosuppresscolorectallivermetastasisbystabilizingddx5stat3cxcl11axis AT xiahu atraupregulatesotud6btorecruitcd8tcellstosuppresscolorectallivermetastasisbystabilizingddx5stat3cxcl11axis AT boshengmei atraupregulatesotud6btorecruitcd8tcellstosuppresscolorectallivermetastasisbystabilizingddx5stat3cxcl11axis AT xiangcheng atraupregulatesotud6btorecruitcd8tcellstosuppresscolorectallivermetastasisbystabilizingddx5stat3cxcl11axis AT xinzhong atraupregulatesotud6btorecruitcd8tcellstosuppresscolorectallivermetastasisbystabilizingddx5stat3cxcl11axis AT chuyicao atraupregulatesotud6btorecruitcd8tcellstosuppresscolorectallivermetastasisbystabilizingddx5stat3cxcl11axis AT zihanchen atraupregulatesotud6btorecruitcd8tcellstosuppresscolorectallivermetastasisbystabilizingddx5stat3cxcl11axis AT huiwang atraupregulatesotud6btorecruitcd8tcellstosuppresscolorectallivermetastasisbystabilizingddx5stat3cxcl11axis AT jinxiangzhang atraupregulatesotud6btorecruitcd8tcellstosuppresscolorectallivermetastasisbystabilizingddx5stat3cxcl11axis |