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Hsa_circRNA_102002 facilitates metastasis of papillary thyroid cancer through regulating miR-488-3p/HAS2 axis.
Cancer Gene Therapy ( IF 4.8 ) Pub Date : 2020-08-29 , DOI: 10.1038/s41417-020-00218-z
Wei Zhang 1 , Ting Liu 2 , Tianshu Li 2 , Xudong Zhao 2
Affiliation  

As important modulators in various physiological processes, circular RNAs (circRNAs) have been increasingly demonstrated in tumors, including papillary thyroid cancer (PTC). Hsa_circRNA_102002 (circ_102002) is a circRNA derived from alternative splicing of ubiquitin-specific peptidase 22 (USP22) transcript, the role of which needs further investigation. Our results suggested the upregulation of circ_102002 in PTC tissues and cells, and its promoting effects on epithelial–mesenchymal transition (EMT) and cell migration. Mechanism studies showed that circ_102002 could sponge microRNA-488-3p (miR-488-3p) and downregulate its expression. The target relationship between miR-488-3p and hyaluronic acid synthetase 2 (HAS2) in PTC was systematically studied. In addition, our results showed that HAS2 overexpression could restore the inhibited cell EMT and migration. Moreover, the inhibitory effect of downregulation of circ_102002 on PTC growth was evaluated in a mouse xenograft model, which involved miR-488-3p and HAS2 regulation. These findings about the signal axis of circ_102002/miR-488-3p/HAS2 may further elucidate the PTC pathogenesis and improve clinical treatment.



中文翻译:

Hsa_circRNA_102002 通过调节 miR-488-3p/HAS2 轴促进甲状腺乳头状癌的转移。

作为各种生理过程中的重要调节剂,环状 RNA (circRNA) 越来越多地在肿瘤中得到证实,包括甲状腺乳头状癌 (PTC)。Hsa_circRNA_102002(circ_102002)是一种来源于泛素特异性肽酶22(USP22)转录物可变剪接的circRNA,其作用需要进一步研究。我们的结果表明 circ_102002 在 PTC 组织和细胞中的上调,及其对上皮-间质转化 (EMT) 和细胞迁移的促进作用。机制研究表明,circ_102002可以海绵microRNA-488-3p(miR-488-3p)并下调其表达。系统研究了 PTC 中 miR-488-3p 与透明质酸合成酶 2 (HAS2) 的靶点关系。此外,我们的结果表明,HAS2 过表达可以恢复受抑制的细胞 EMT 和迁移。此外,在小鼠异种移植模型中评估了 circ_102002 下调对 PTC 生长的抑制作用,该模型涉及 miR-488-3p 和 HAS2 调节。这些关于circ_102002/miR-488-3p/HAS2信号轴的发现可能会进一步阐明PTC的发病机制并改善临床治疗。

更新日期:2020-08-29
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