The role of G-Quadruplex DNA in Paraspeckle formation in cancer

作者：Uditi Bhatt; Amy L. Kretzmann; Aurore Guédin; Arnold Ou; Simon Kobelke; Charles S. Bond; Cameron W. Evans; Laurence H. Hurley; Jean-Louis Mergny; K. Swaminathan Iyer; Archa H. Fox; Nicole M. Smith^*

来源：Biochimie, 2021, 190: 124-131.

DOI：10.1016/j.biochi.2021.07.008

• G-quadruplex
• G4 DNA
• G-quartet
• G-tetraplex
• Paraspeckles
• NEAT1
• NEAT1_2
• Breast cancer

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.

• 单位
  The University of western Australia; The University of Western Australia; the university of western australia