Yang Hongbo, Peng Zhibin, Liang Min, Zhang Yubo, Wang Yangyang, Huang Tianwen, Jiang Yudong, Jiang Bo, Wang Yansong
Department of Orthopaedic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Oncotarget. 2018 Jan 5;9(38):25285-25293. doi: 10.18632/oncotarget.23935. eCollection 2018 May 18.
Quaking(QKI) is an RNA binding protein, and it has been shown to serve as a tumor suppressor. However, the expression and functions of QKI in osteosarcoma progression remain poorly understood. In this study, we aimed to explore the expression of QKI2 in osteosarcoma tissues and to determine the mechanisms underlying aberrant QKI2 expression and the effect of QKI2 on osteosarcoma progression. We found that QKI2 was significantly down-regulated in osteosarcoma tissues compared with adjacent normal bone tissues. Using a series of molecular biological techniques, we demonstrated that all members of the miR-17-92 cluster were up-regulated and contributed to the down-regulation of QKI2 expression in osteosarcoma. Functional examination showed that QKI2 inhibited the proliferation, migration and invasion of osteosarcoma cells via decreasing the expression of β-catenin. Conclusively, we revealed that the regulatory axis consisting of the miR-17-92 cluster/QKI2/β-catenin plays a crucial role in the development and progression of osteosarcoma.
颤抖蛋白(QKI)是一种RNA结合蛋白,已被证明具有肿瘤抑制作用。然而,QKI在骨肉瘤进展中的表达和功能仍知之甚少。在本研究中,我们旨在探讨QKI2在骨肉瘤组织中的表达,确定QKI2异常表达的机制以及QKI2对骨肉瘤进展的影响。我们发现,与相邻正常骨组织相比,QKI2在骨肉瘤组织中显著下调。通过一系列分子生物学技术,我们证明miR-17-92簇的所有成员均上调,并导致骨肉瘤中QKI2表达下调。功能检测表明,QKI2通过降低β-连环蛋白的表达来抑制骨肉瘤细胞的增殖、迁移和侵袭。总之,我们揭示了由miR-17-92簇/QKI2/β-连环蛋白组成的调控轴在骨肉瘤的发生和进展中起关键作用。