| First Author | Li W | Year | 2019 |
| Journal | Cell Commun Signal | Volume | 17 |
| Issue | 1 | Pages | 162 |
| PubMed ID | 31823782 | Mgi Jnum | J:380228 |
| Mgi Id | MGI:6730480 | Doi | 10.1186/s12964-019-0484-6 |
| Citation | Li W, et al. (2019) TRIM30 modulates Interleukin-22-regulated papillary thyroid Cancer cell migration and invasion by targeting Sox17 for K48-linked Polyubiquitination. Cell Commun Signal 17(1):162 |
| abstractText | BACKGROUND: Interleukin-22 (IL-22) belongs to the IL-10 cytokine family and is mainly produced by activated Th1 cells. Although IL-22 expression is reported to be elevated in many cancers, and increased IL-22 expression correlates with tumor progression and poor prognosis, little is known about the role of IL-22 in papillary thyroid cancer (PTC). We previously demonstrated that IL-22 promotes PTC cell migration and invasion through the microRNA-595/Sox17 axis. METHODS: We used qRT-PCR and western blot to determine TRIM30, Sox17 and beta-catenin expression in PTC cells. Knockdown and overexpression were performed to detect the role of TRIM30/Sox17/beta-catenin axis on the migration and invasion PTC cells. Co-IP were used to determine the interaction between TRIM30 and Sox17. FINDINGS: In this study, we demonstrated that IL-22 triggered tripartite-motif protein 30 (TRIM30) association with Sox17, thereby mediating K48-linked polyubiquitination of Sox17. We then demonstrated that TRIM30 was a positive regulator of IL-22-regulated migration and invasion of PTC cells. We also found that IL-22 induced the transcriptional activity of beta-catenin and translocation of beta-catenin from cytosol to the nucleus. Upon investigating the mechanisms behind this event, we found that IL-22 disrupted Sox17/beta-catenin interactions by inducing TRIM30/Sox17 interactions, leading to promotion of beta-catenin-dependent signaling. The analysis of hundreds of clinical specimens revealed that IL-22, TRIM30 and beta-catenin levels were upregulated in PTC tissues compared with normal thyroid, and that their expression levels were closely correlated. Taken together, under the influence of IL-22, by sequestration of Sox17, TRIM30 promotes beta-catenin-dependent signaling that promotes PTC cell proliferation. |
