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Published on: August 23, 2019
TRIM30 modulates Interleukin-22-regulated papillary thyroid Cancer cell migration and invasion by targeting Sox17 for
Wei Li1, Fen Li2, Weiwei Lei1
1Department of Otolaryngology Head and Neck Surgery, Remin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, the, People's Republic of China.
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 β-catenin expression in PTC cells. Knockdown and overexpression were performed to detect the role of TRIM30/Sox17/β-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 β-catenin and translocation of β-catenin from cytosol to the nucleus. Upon investigating the mechanisms behind this event, we found that IL-22 disrupted Sox17/β-catenin interactions by inducing TRIM30/Sox17 interactions, leading to promotion of β-catenin-dependent signaling. The analysis of hundreds of clinical specimens revealed that IL-22, TRIM30 and β-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 β-catenin-dependent signaling that promotes PTC cell proliferation.
