Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
Biomed Pharmacother. 2020 Jan;121:109248. doi: 10.1016/j.biopha.2019.109248. Epub 2019 Nov 14.
LncRNA NEAT1 is reported as a crucial oncogene in multiple cancers. But, its biological role in bladder cancer is barely understood. Therefore, we concentrated on the function and role of NEAT1 in bladder cancer. Firstly, NEAT1 expression in bladder cancer cells was determined and it was displayed NEAT1 was significant elevated. NEAT1 was knockdown and overexpressed in T24 and J82 cells. Then it was indicated that NEAT1 silence greatly inhibited bladder cancer cell proliferation with an increased ratio of apoptotic cells and severe cell cycle arrest. Overexpression of NEAT1 exhibited a reversed process in bladder cancer cells. Additionally, in vivo experiments were employed using establishment of nude mice models. NEAT1 knockdown inhibited bladder cancer growth while increase of NEAT1 promoted bladder cancer development in vivo. By employing the bioinformatics analysis, we speculated that miR-410 was as a downstream target of NEAT1. Then, the targeting association between them was proved in our research and we implicated miR-410 was dramatically restrained in bladder cancer cells. Meanwhile, it was exhibited that miR-410 was negatively regulated by NEAT1. Apart from these, HMGB1 was speculated as a downstream target of miR-410. Dual-luciferase reporter assay was used to prove the correlation between miR-410 and HMGB1. Up-regulation of miR-410 restrained HMGB1 levels and NEAT1 can regulate HMGB1 level via sponging miR-410. To sum up, we implied NEAT1/miR-410/HMGB1 axis participated in bladder cancer.
LncRNA NEAT1 被报道为多种癌症中的关键癌基因。但是，其在膀胱癌中的生物学作用还知之甚少。因此，我们专注于 NEAT1 在膀胱癌中的功能和作用。首先，确定了膀胱癌细胞中的 NEAT1 表达，结果显示 NEAT1 显著升高。在 T24 和 J82 细胞中敲低和过表达 NEAT1。结果表明，NEAT1 沉默显著抑制膀胱癌细胞增殖，凋亡细胞比例增加，细胞周期严重阻滞。过表达 NEAT1 在膀胱癌细胞中表现出相反的过程。此外，还通过建立裸鼠模型进行了体内实验。NEAT1 敲低抑制膀胱癌生长，而增加 NEAT1 促进体内膀胱癌的发展。通过生物信息学分析，我们推测 miR-410 是 NEAT1 的下游靶标。然后，在我们的研究中证明了它们之间的靶向关联，并表明 miR-410 在膀胱癌细胞中显著受到抑制。同时，表明 miR-410 受 NEAT1 的负调控。除此之外，还推测 HMGB1 是 miR-410 的下游靶标。双荧光素酶报告基因实验证明了 miR-410 和 HMGB1 之间的相关性。上调 miR-410 抑制 HMGB1 水平，而 NEAT1 可以通过海绵吸附 miR-410 来调节 HMGB1 水平。总之，我们暗示 NEAT1/miR-410/HMGB1 轴参与了膀胱癌的发生。
