LINC01605 Is a Novel Target of Mutant p53 in Breast and Ovarian Cancer Cell Lines.

Autor: Coan, Michela, Toso, Martina, Cesaratto, Laura, Rigo, Ilenia, Borgna, Silvia, Dalla Pietà, Anna, Zandonà, Luigi, Iuri, Lorenzo, Zucchetto, Antonella, Piazza, Carla, Baldassarre, Gustavo, Spizzo, Riccardo, Nicoloso, Milena Sabrina
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Zdroj: International Journal of Molecular Sciences; Sep2023, Vol. 24 Issue 18, p13736, 15p
Abstrakt: TP53 is the most frequently mutated gene in human cancers. Most TP53 genomic alterations are missense mutations, which cause a loss of its tumour suppressor functions while providing mutant p53 (mut_p53) with oncogenic features (gain-of-function). Loss of p53 tumour suppressor functions alters the transcription of both protein-coding and non-protein-coding genes. Gain-of-function of mut_p53 triggers modification in gene expression as well; however, the impact of mut_p53 on the transcription of the non-protein-coding genes and whether these non-protein-coding genes affect oncogenic properties of cancer cell lines are not fully explored. In this study, we suggested that LINC01605 (also known as lincDUSP) is a long non-coding RNA regulated by mut_p53 and proved that mut_p53 directly regulates LINC01605 by binding to an enhancer region downstream of the LINC01605 locus. We also showed that the loss or downregulation of LINC01605 impairs cell migration in a breast cancer cell line. Eventually, by performing a combined analysis of RNA-seq data generated in mut_TP53-silenced and LINC01605 knockout cells, we showed that LINC01605 and mut_p53 share common gene pathways. Overall, our findings underline the importance of ncRNAs in the mut_p53 network in breast and ovarian cancer cell lines and in particular the importance of LINC01605 in mut_p53 pro-migratory pathways. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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