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.

中文翻译：

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TRIM30通过将Sox17靶向K48连接的多聚泛素化来调节白介素22调节的甲状腺乳头状甲状腺癌细胞的迁移和侵袭。

背景技术白介素22（IL-22）属于IL-10细胞因子家族，主要由活化的Th1细胞产生。尽管据报道IL-22表达在许多癌症中升高，并且IL-22表达增加与肿瘤进展和不良预后相关，但对于IL-22在甲状腺乳头状癌（PTC）中的作用知之甚少。我们先前证明，IL-22通过microRNA-595 / Sox17轴促进PTC细胞迁移和侵袭。方法我们使用qRT-PCR和Western印迹法测定PTC细胞中TRIM30，Sox17和β-catenin的表达。进行了基因敲低和过表达，以检测TRIM30 / Sox17 /β-catenin轴在PTC细胞迁移和侵袭中的作用。Co-IP用于确定TRIM30和Sox17之间的相互作用。调查结果 我们证明IL-22触发了与Sox17的三方基序蛋白30（TRIM30）缔合，从而介导了K48连锁的Sox17多聚泛素化。然后，我们证明了TRIM30是IL-22调节的PTC细胞迁移和侵袭的正调节剂。我们还发现IL-22诱导了β-catenin的转录活性和β-catenin从细胞质到核的转运。在调查此事件背后的机制后，我们发现IL-22通过诱导TRIM30 / Sox17相互作用破坏了Sox17 /β-catenin相互作用，从而促进了β-catenin依赖性信号传导。对数百份临床标本进行的分析表明，与正常甲状腺相比，PTC组织中的IL-22，TRIM30和β-连环蛋白水平上调，并且它们的表达水平密切相关。在一起