Paraspeckles are RNA–protein structures within the nucleus of mammalian cells, capable of orchestrating various biochemical processes. An overexpression of the architectural component of paraspeckles, a long non-coding RNA called NEAT1 (Nuclear Enriched Abundant Transcript 1), has been linked to a variety of cancers and is often associated with poor patient prognosis. Thus, there is an accumulating interest in the role of paraspeckles in carcinogenesis, however there is a limited understanding of how NEAT1 expression is regulated. Here, we demonstrate that both nuclear G-quadruplex (G4) and paraspeckle formation are significantly increased in a human breast cancer cell line compared to non-tumorigenic breast cells. Moreover, we identified and characterized G4-forming sequences within the NEAT1 promoter and demonstrate stabilization of G4 DNA with a G4-stabilizing small molecule results in a significant alteration in both paraspeckle formation and NEAT1 expression. This G4-mediated alteration of NEAT1 at both the transcriptional and post-transcriptional levels was evident in U2OS osteosarcoma cells, MCF-7 breast adenocarcinoma and MDA-MB-231 triple negative breast cancer cells.

副啄木鸟是哺乳动物细胞核内的 RNA 蛋白质结构，能够协调各种生化过程。副啄木鸟的结构成分过表达，一种称为 NEAT1（富含核的丰富转录本 1）的长非编码 RNA，与多种癌症有关，并且通常与患者预后不良有关。因此，人们对副啄木鸟在致癌作用中的作用越来越感兴趣，但对NEAT1表达是如何调节的了解有限。在这里，我们证明了与非致瘤性乳腺细胞相比，人类乳腺癌细胞系中的核 G-四链体 (G4) 和副啄木鸟的形成均显着增加。此外，我们在NEAT1中识别并表征了 G4 形成序列启动子并证明 G4 DNA 与 G4 稳定小分子的稳定性导致 paraspeckle 形成和NEAT1表达的显着改变。这种 G4 介导的 NEAT1 在转录和转录后水平的改变在 U2OS 骨肉瘤细胞、MCF-7 乳腺癌和 MDA-MB-231 三阴性乳腺癌细胞中很明显。