Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
J Cell Physiol. 2020 Feb;235(2):1120-1128. doi: 10.1002/jcp.29025. Epub 2019 Jul 11.
The long noncoding RNA MEG3 is a significant tumor-suppressive gene in various tumors. But its biological role in bladder cancer remains uninvestigated. Herein, the biological mechanism of MEG3 in bladder cancer pathogenesis was explored. First, the expression of MEG3 in bladder cancer cells was examined, and we found that it was significantly reduced. In addition, in bladder cancer cells, we observed htat miR-494 was increased. Then, MEG3 was overexpressed in UMUC3 and SW780 cells and it could negatively modulate miR-494 expression. Bladder cancer cell proliferation was repressed, cell apoptosis was triggered and meanwhile, the cell cycle was remarkably arrested by the overexpression of MEG3. Moreover, the increase of MEG3 suppressed bladder cancer cell migration and invasion capacity. MEG3 can sponge miR-494 and the binding sites between them were confirmed by carrying out a series of functional assays. Furthermore, PTEN was speculated as a putative target of miR-494. Meanwhile, we found that miR-494 inhibitors induced PTEN. Finally, in vivo assays were conducted to prove that MEG3 can restrain bladder tumor growth by modulating miR-494 and PTEN. In conclusion, it was suggested MEG3 can interact with miR-494 to regulate PTEN in bladder cancer development.
长链非编码 RNA MEG3 是多种肿瘤中重要的肿瘤抑制基因。但其在膀胱癌中的生物学作用尚未被研究。本研究旨在探索 MEG3 在膀胱癌发病机制中的生物学机制。首先，检测了膀胱癌细胞中 MEG3 的表达情况，发现其表达显著降低。此外，在膀胱癌细胞中，观察到 miR-494 增加。然后，在 UMUC3 和 SW780 细胞中过表达 MEG3，发现其可负调控 miR-494 的表达。过表达 MEG3 可抑制膀胱癌细胞增殖，诱导细胞凋亡，同时显著阻滞细胞周期。此外，MEG3 的增加抑制了膀胱癌细胞的迁移和侵袭能力。MEG3 可作为 miR-494 的海绵分子，通过一系列功能实验证实了它们之间的结合位点。进一步推测 miR-494 的靶基因是 PTEN。同时，我们发现 miR-494 抑制剂可诱导 PTEN 表达。最后，进行了体内实验，证明 MEG3 可以通过调节 miR-494 和 PTEN 来抑制膀胱癌肿瘤的生长。总之，研究结果表明 MEG3 可通过与 miR-494 相互作用来调节膀胱癌发生发展中的 PTEN。
