TRIM30 modulates Interleukin-22-regulated papillary thyroid Cancer cell migration and invasion by targeting Sox17 for K48-linked Polyubiquitination.

ABSTRACT: 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 ?-catenin expression in PTC cells. Knockdown and overexpression were performed to detect the role of TRIM30/Sox17/?-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 ?-catenin and translocation of ?-catenin from cytosol to the nucleus. Upon investigating the mechanisms behind this event, we found that IL-22 disrupted Sox17/?-catenin interactions by inducing TRIM30/Sox17 interactions, leading to promotion of ?-catenin-dependent signaling. The analysis of hundreds of clinical specimens revealed that IL-22, TRIM30 and ?-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 ?-catenin-dependent signaling that promotes PTC cell proliferation.

SUBMITTER: Li W 

PROVIDER: S-EPMC6902597 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature