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

0555745 - BFÚ 2022 RIV FR eng J - Journal Article
Bhatt, U. - Kretzmann, A. - Guédin, A. - Ou, A. - Kobelke, S. - Bond, C. - Evans, C. - Hurley, L. - Mergny, Jean-Louis - Iyer, K. - Fox, A.H. - Smith, N.
The role of G-Quadruplex DNA in Paraspeckle formation in cancer.
Biochimie. Roč. 190, NOV 2021 (2021), s. 124-131. ISSN 0300-9084. E-ISSN 1638-6183
R&D Projects: GA MŠMT EF15_003/0000477
Institutional support: RVO:68081707
Keywords : long noncoding rna * gene-expression * stress-response * down-regulation * breast-cancer * lncrna neat1 * progression
OECD category: Biochemistry and molecular biology
Impact factor: 4.372, year: 2021
Method of publishing: Limited access
https://www.sciencedirect.com/science/article/pii/S0300908421001826?via%3Dihub

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 nontumorigenic 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. (c) 2021 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.
Permanent Link: http://hdl.handle.net/11104/0330206