Tripartite motif 47 promotes the development of thyroid carcinoma through ADAR ubiquitination.

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.