Tripartite motif 47 promotes the development of thyroid carcinoma through ADAR ubiquitination
Abstract Background Tripartite motif 47 (TRIM47) plays a vital role in the carcinogenesis and drug resistance of various cancers, whereas the function of TRIM47 in thyroid carcinoma (TC) remains unclear. Methods Human study and animal experiments were performed. Mass spectrometry, cellular invasion/...
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BMC
2025-07-01
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| Series: | Molecular Medicine |
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| Online Access: | https://doi.org/10.1186/s10020-025-01298-z |
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| author | Hongzhou Liu Xiaodong Hu Tan Li Yuhan Wang Xiaomin Fu |
| author_facet | Hongzhou Liu Xiaodong Hu Tan Li Yuhan Wang Xiaomin Fu |
| author_sort | Hongzhou Liu |
| collection | DOAJ |
| description | Abstract Background Tripartite motif 47 (TRIM47) plays a vital role in the carcinogenesis and drug resistance of various cancers, whereas the function of TRIM47 in thyroid carcinoma (TC) remains unclear. Methods Human study and animal experiments were performed. Mass spectrometry, cellular invasion/metastasis assay, chemo-resistance assay, and ubiquitination evaluation were conducted to investigate the interaction between TRIM47 and adenosine deaminases acting on RNA (ADAR). Results TRIM47 expression was increased in human tissues and cell lines of TC. Functional experiments demonstrated that TRIM47 expression enhanced malignant biological behaviors. With mass spectrometry, TRIM47 silencing could significantly decrease the chemo-resistance of TC cells to chemotherapeutic drugs. The interaction between TRIM47 and ADAR was mediated through the ubiquitin–proteasome pathway (UPP), which was approved by RNA interference procedure and co-immunoprecipitation. Conclusion Comprehensively, glycogen synthase kinase-3β (GSK-3β)-associated ubiquitination is critical in the TRIM47-ADAR-GSK-3β axis. This study demonstrates that TRIM47 interacted with ADAR to facilitate ADAR protein degradation via ubiquitination and GSK-3β-associated phosphorylation, which serves as a novel therapeutic avenue for TC. Graphical Abstract |
| format | Article |
| id | doaj-art-8818cdc8f3dd4e18a5ea294010cd6ade |
| institution | Kabale University |
| issn | 1528-3658 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj-art-8818cdc8f3dd4e18a5ea294010cd6ade2025-08-20T04:01:34ZengBMCMolecular Medicine1528-36582025-07-0131111710.1186/s10020-025-01298-zTripartite motif 47 promotes the development of thyroid carcinoma through ADAR ubiquitinationHongzhou Liu0Xiaodong Hu1Tan Li2Yuhan Wang3Xiaomin Fu4Department of Endocrinology, First Hospital of Handan CityDepartment of Endocrinology, The First Medical Center, Chinese PLA General HospitalDepartment of Endocrinology, The First Medical Center, Chinese PLA General HospitalDepartment of Endocrinology, The First Medical Center, Chinese PLA General HospitalClinics of Cadre, Department of Outpatient, The First Medical Center, Chinese PLA General HospitalAbstract Background Tripartite motif 47 (TRIM47) plays a vital role in the carcinogenesis and drug resistance of various cancers, whereas the function of TRIM47 in thyroid carcinoma (TC) remains unclear. Methods Human study and animal experiments were performed. Mass spectrometry, cellular invasion/metastasis assay, chemo-resistance assay, and ubiquitination evaluation were conducted to investigate the interaction between TRIM47 and adenosine deaminases acting on RNA (ADAR). Results TRIM47 expression was increased in human tissues and cell lines of TC. Functional experiments demonstrated that TRIM47 expression enhanced malignant biological behaviors. With mass spectrometry, TRIM47 silencing could significantly decrease the chemo-resistance of TC cells to chemotherapeutic drugs. The interaction between TRIM47 and ADAR was mediated through the ubiquitin–proteasome pathway (UPP), which was approved by RNA interference procedure and co-immunoprecipitation. Conclusion Comprehensively, glycogen synthase kinase-3β (GSK-3β)-associated ubiquitination is critical in the TRIM47-ADAR-GSK-3β axis. This study demonstrates that TRIM47 interacted with ADAR to facilitate ADAR protein degradation via ubiquitination and GSK-3β-associated phosphorylation, which serves as a novel therapeutic avenue for TC. Graphical Abstracthttps://doi.org/10.1186/s10020-025-01298-zThyroid carcinomaTripartite motif 47Adenosine deaminases acting on RNAGlycogen synthase kinase-3βUbiquitinationPhosphorylation |
| spellingShingle | Hongzhou Liu Xiaodong Hu Tan Li Yuhan Wang Xiaomin Fu Tripartite motif 47 promotes the development of thyroid carcinoma through ADAR ubiquitination Molecular Medicine Thyroid carcinoma Tripartite motif 47 Adenosine deaminases acting on RNA Glycogen synthase kinase-3β Ubiquitination Phosphorylation |
| title | Tripartite motif 47 promotes the development of thyroid carcinoma through ADAR ubiquitination |
| title_full | Tripartite motif 47 promotes the development of thyroid carcinoma through ADAR ubiquitination |
| title_fullStr | Tripartite motif 47 promotes the development of thyroid carcinoma through ADAR ubiquitination |
| title_full_unstemmed | Tripartite motif 47 promotes the development of thyroid carcinoma through ADAR ubiquitination |
| title_short | Tripartite motif 47 promotes the development of thyroid carcinoma through ADAR ubiquitination |
| title_sort | tripartite motif 47 promotes the development of thyroid carcinoma through adar ubiquitination |
| topic | Thyroid carcinoma Tripartite motif 47 Adenosine deaminases acting on RNA Glycogen synthase kinase-3β Ubiquitination Phosphorylation |
| url | https://doi.org/10.1186/s10020-025-01298-z |
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