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SPRY4内含子转录本1通过与骨肉瘤中的Snail1结合促进上皮-间质转化

SPRY4 Intronic Transcript 1 Promotes Epithelial-Mesenchymal Transition Through Association with Snail1 in Osteosarcoma.

作者信息

Ru Neng, Liang Jie, Zhang Fan, Wu Weifei, Wang Feifan, Liu Xinzong, Du Yuanli

机构信息

Department of Orthopedics, The People's Hospital of Three Gorges University , Yichang, China .

出版信息

DNA Cell Biol. 2016 Jun;35(6):290-5. doi: 10.1089/dna.2016.3226. Epub 2016 Mar 16.

Abstract

Osteosarcoma is an aggressive tumor and the most common malignancy of the skeleton. Due to pulmonary metastasis, the 5-year survival rate is still unsatisfactory. It has been reported that SPRY4 intronic transcript 1 (SPRY4-IT1) promotes cell growth, invasion, and inhibits apoptosis in several cancers. However, the role of SPRY4-IT1 in osteosarcoma remains unclear. In the present study, we investigated the role of SPRY4-IT1 in osteosarcoma cells. Loss- and gain-of-function assays demonstrated that SPRY4-IT1 promoted cell proliferation, migration, and invasion in osteosarcoma. Moreover, SPRY4-IT1 induced epithelial-mesenchymal transition phenotype in osteosarcoma cells. Subsequent investigations revealed that SPRY4-IT1 promoted migration and invasion through association with Snail1 and regulating its stability. Based on these findings, the SPRY4-IT1/Snail1/E-cadherin pathway may play a crucial role in promoting osteosarcoma metastasis. Thus, SPRY4-IT1 may be a potential target for new therapies of osteosarcoma.

摘要

骨肉瘤是一种侵袭性肿瘤,也是骨骼最常见的恶性肿瘤。由于肺转移,其5年生存率仍不尽人意。据报道,SPRY4内含子转录本1(SPRY4-IT1)在多种癌症中促进细胞生长、侵袭并抑制细胞凋亡。然而,SPRY4-IT1在骨肉瘤中的作用仍不清楚。在本研究中,我们调查了SPRY4-IT1在骨肉瘤细胞中的作用。功能缺失和功能获得实验表明,SPRY4-IT1促进骨肉瘤细胞的增殖、迁移和侵袭。此外,SPRY4-IT1诱导骨肉瘤细胞发生上皮-间质转化表型。随后的研究表明,SPRY4-IT1通过与Snail1结合并调节其稳定性来促进迁移和侵袭。基于这些发现,SPRY4-IT1/Snail1/E-钙黏蛋白通路可能在促进骨肉瘤转移中起关键作用。因此,SPRY4-IT1可能是骨肉瘤新疗法的潜在靶点。

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