TRIM14 regulates cell proliferation and invasion in osteosarcoma via promotion of the AKT signaling pathway.
TRIM14 regulates cell proliferation and invasion in osteosarcoma via promotion of the AKT signaling pathway.
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DOI：
10.1038/srep42411
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发表时间：
2017-02-16
影响因子：
4.6
通讯作者：
Kang Y
中科院分区：
文献类型：
--
作者：
Xu G;Guo Y;Xu D;Wang Y;Shen Y;Wang F;Lv Y;Song F;Jiang D;Zhang Y;Lou Y;Meng Y;Yang Y;Kang Y
最近的研究表明，包含三重基序的蛋白（TRIM）家族的一些成员作为肿瘤发生的重要调节因子。然而，TRIM14在骨肉瘤中的生物学作用仍有待确定。在这项研究中，我们发现TRIM14在人骨肉瘤标本和细胞系中上调，并与骨肉瘤进展和较短的患者生存时间相关。功能研究表明，TRIM14的过表达在体外可促进骨肉瘤细胞的增殖、克隆形成、细胞周期进程、迁移和侵袭，在体内可促进肿瘤生长，而其沉默则相反。此外，TRIM14过表达诱导AKT通路的激活。抑制AKT表达逆转了TRIM14介导的对细胞生长和迁移的促进作用，以及TRIM14诱导的上皮细胞向间质细胞转化（EMT）和细胞周期蛋白D1上调。我们的研究结果共同表明，TRIM14通过上调骨肉瘤细胞中的AKT信号通路作为癌基因发挥作用，支持其作为这种疾病的治疗靶点的潜在效用。
Recent studies have shown that some members of the tripartite motif-containing protein (TRIM) family serve as important regulators of tumorigenesis. However, the biological role of TRIM14 in osteosarcoma remains to be established. In this study, we showed that TRIM14 is upregulated in human osteosarcoma specimens and cell lines, and correlated with osteosarcoma progression and shorter patient survival times. Functional studies demonstrated that overexpression of TRIM14 enhances osteosarcoma cell proliferation, clone formation, cell cycle procession, migration and invasion in vitro and promotes tumor growth in vivo, and conversely, its silencing has the opposite effects. Furthermore, TRIM14 overexpression induced activation of the AKT pathway. Inhibition of AKT expression reversed the TRIM14-mediated promotory effects on cell growth and mobility, in addition to TRIM14-induced epithelial-to-mesenchymal transition (EMT) and cyclin D1 upregulation. Our findings collectively suggest that TRIM14 functions as an oncogene by upregulating the AKT signaling pathway in osteosarcoma cells, supporting its potential utility as a therapeutic target for this disease.