Department of Clinical Laboratory, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Department of Clinical Laboratory, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
J Cell Physiol. 2021 Jan;236(1):121-130. doi: 10.1002/jcp.29644. Epub 2020 Aug 16.
Long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) is regarded as an oncogene in multiple cancers. Previous studies have shown that NEAT1 is involved in the proliferation and tumorigenesis of glioma cells, while miR-185-5p functions as a tumor suppressor in glioma. However, the underlying molecular mechanism of NEAT1 in glioma, especially in association with miR-185-5p, has not been studied. In this study, we first demonstrated that NEAT1 expression was upregulated, and miR-185-5p downregulated in glioma tissues and cells. More important, NEAT1 expression was negatively correlated with miR-185-5p expression in glioma tissues. In vitro and in vivo experiments verified that NEAT1 was a competing endogenous RNA for miR-185-5p for promoting DNA methyltransferase 1 (DNMT1) expression and activated mammalian target of rapamycin (mTOR) signaling, thus inhibiting apoptosis, and promoting glioma migration, proliferation, and epithelial-mesenchymal transition process. Furthermore, NEAT1 knockdown suppressed tumor growth and reduced the expression of proliferation antigen Ki-67, DNMT1, and mTOR, but upregulated the expression of miR-185-5p in vivo. Finally, with mTOR inhibitor rapamycin, we confirmed that NEAT1 promoted glioma activity through mTOR signaling both in vitro and in vivo. In conclusion, these results suggest that NEAT1 promotes glioma tumorigenesis via miR-185-5p/DNMT1/mTOR signaling, which may provide a new target for the diagnosis and therapy of glioma.
长链非编码 RNA 核斑组装转录本 1（NEAT1）被认为是多种癌症中的癌基因。先前的研究表明，NEAT1 参与了神经胶质瘤细胞的增殖和肿瘤发生，而 miR-185-5p 在神经胶质瘤中作为一种肿瘤抑制因子发挥作用。然而，NEAT1 在神经胶质瘤中的潜在分子机制，特别是与 miR-185-5p 的关联，尚未得到研究。在这项研究中，我们首先证明了 NEAT1 的表达在神经胶质瘤组织和细胞中上调，而 miR-185-5p 下调。更重要的是，NEAT1 的表达与神经胶质瘤组织中 miR-185-5p 的表达呈负相关。体外和体内实验验证了 NEAT1 是 miR-185-5p 的竞争性内源性 RNA，可促进 DNA 甲基转移酶 1（DNMT1）的表达并激活哺乳动物雷帕霉素靶蛋白（mTOR）信号通路，从而抑制细胞凋亡，并促进神经胶质瘤的迁移、增殖和上皮-间充质转化过程。此外，NEAT1 敲低抑制肿瘤生长并降低增殖抗原 Ki-67、DNMT1 和 mTOR 的表达，但体内上调 miR-185-5p 的表达。最后，用 mTOR 抑制剂雷帕霉素，我们在体外和体内证实了 NEAT1 通过 mTOR 信号促进神经胶质瘤的活性。总之，这些结果表明，NEAT1 通过 miR-185-5p/DNMT1/mTOR 信号促进神经胶质瘤的肿瘤发生，这可能为神经胶质瘤的诊断和治疗提供新的靶点。
