Upregulation of Long Noncoding RNA TUG1 Promotes Bladder Cancer Cell Proliferation, Migration, and Invasion by Inhibiting miR-29c.
Upregulation of Long Noncoding RNA TUG1 Promotes Bladder Cancer Cell Proliferation, Migration, and Invasion by Inhibiting miR-29c.
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DOI：
10.3727/096504018x15152085755247
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发表时间：
2018-08-23
影响因子：
3.1
通讯作者：
Guan Y
中科院分区：
文献类型：
--
作者：
Guo P;Zhang G;Meng J;He Q;Li Z;Guan Y
膀胱癌是世界上与癌症相关的死亡的主要原因之一。长非编码RNA(LncRNA)牛磺酸上调基因1(TUG1)在包括BC在内的多种肿瘤的发生发展中起重要作用。然而，TUG1在调控BC进展中的确切作用仍然知之甚少。在本研究中，我们发现TUG1在BC组织和细胞系中表达上调，microRNA-29c(miR-29c)表达下调。TUG1过表达促进T24和EJ细胞的增殖，而TUG1基因下调则相反。TUG1的上调明显促进了T24和EJ细胞的迁移和侵袭。相反，TUG1沉默抑制了T24和EJ细胞的迁移和侵袭。此外，TUG1基因敲除显著增加了miR-29c在体外的表达。相反，过表达TUG1显著降低miR-29c的表达。携带突变型TUG1基因的重组表达载体对miR-29c的表达无明显影响。MiR-29c与TUG1的结合部位存在直接相互作用。此外，针对TUG1的小干扰RNA对BC细胞的增殖、迁移和侵袭的抑制作用可被miR-29c下调所逆转。总之，我们的研究有力地证明了TUG1通过抑制miR-29c来促进BC细胞的增殖、迁移和侵袭，表明lncRNA TUG1可能是BC基因治疗的一个有前途的靶点。
Bladder cancer (BC) is one of the leading causes of cancer-related deaths in the world. Long noncoding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) plays an important role in the development and progression of numerous cancers, including BC. However, the exact role of TUG1 in modulating BC progression is still poorly known. In this study, we found that TUG1 was upregulated and microRNA-29c (miR-29c) was downregulated in BC tissues and cell lines. Overexpression of TUG1 promoted the cell proliferation of T24 and EJ cells, whereas TUG1 knockdown had the opposite effect. Upregulation of TUG1 obviously facilitated the migration and invasion of T24 and EJ cells. In contrast, TUG1 silencing repressed the migration and invasion of T24 and EJ cells. Furthermore, TUG1 knockdown markedly increased the expression of miR-29c in vitro. On the contrary, overexpression of TUG1 remarkably decreased the expression of miR-29c. Transfection with plasmids containing mutant TUG1 has no effect on the expression of miR-29c. There were direct interactions between miR-29c and the binding sites of TUG1. In addition, the inhibitory effects of small interfering RNA specific for TUG1 on BC cell proliferation, migration, and invasion were reversed by downregulation of miR-29c. Collectively, our study strongly demonstrates that TUG1 promotes BC cell proliferation, migration, and invasion by inhibiting miR-29c, suggesting that lncRNA TUG1 may be a promising target for BC gene therapy.