Ru Neng, Liang Jie, Zhang Fan, Wu Weifei, Wang Feifan, Liu Xinzong, Du Yuanli
Department of Orthopedics, The People's Hospital of Three Gorges University , Yichang, China .
DNA Cell Biol. 2016 Jun;35(6):290-5. doi: 10.1089/dna.2016.3226. Epub 2016 Mar 16.
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.
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。
