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Updated: Jul 15, 2025
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
LINC01605 Is a Novel Target of Mutant p53 in Breast and Ovarian Cancer Cell Lines
Michela Coan1, Martina Toso1, Laura Cesaratto1
1Division of Molecular Oncology, Department of Translational Research, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Via Franco Gallini 2, 33081 Aviano, Italy.
Abstract:
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.
Insights
Mutant TP53 (mut_p53) oncogenic functions involve the long non-coding RNA LINC01605. This study shows mut_p53 directly regulates LINC01605, impacting cell migration and sharing gene pathways in cancer cells.
Area of Science:
- Molecular Biology
- Cancer Genetics
- Non-coding RNA Research
Background:
- TP53 is frequently mutated in human cancers, with missense mutations conferring oncogenic gain-of-function (GOF) properties to mutant p53 (mut_p53).
- While mut_p53 affects protein-coding gene expression, its impact on non-coding RNAs and their role in cancer remains less understood.
- Investigating the regulatory network of mut_p53, particularly involving long non-coding RNAs (lncRNAs), is crucial for understanding cancer progression.
Purpose of the Study:
- To investigate the role of the lncRNA LINC01605 in cancers with mutations in the TP53 gene.
- To determine if mut_p53 directly regulates LINC01605 transcription.
- To elucidate the functional impact of LINC01605 on cancer cell properties, such as migration, and its relationship with mut_p53 pathways.
Main Methods:
- RNA sequencing (RNA-seq) analysis of cancer cell lines with silenced mut_p53 and LINC01605 knockout.
- Chromatin immunoprecipitation (ChIP) to assess mut_p53 binding to the LINC01605 locus.
- Cell migration assays to evaluate the functional role of LINC01605.
Main Results:
- Mutant p53 (mut_p53) directly binds to an enhancer region, regulating the transcription of LINC01605.
- Downregulation or loss of LINC01605 impairs cell migration in breast cancer cell lines.
- Combined analysis revealed shared gene pathways between LINC01605 and mut_p53 networks.
Conclusions:
- LINC01605 is a novel target regulated by mut_p53, highlighting the importance of lncRNAs in the mut_p53 oncogenic network.
- LINC01605 plays a significant role in promoting cell migration, contributing to the pro-migratory effects of mut_p53.
- These findings offer potential therapeutic targets within the mut_p53-LINC01605 axis in breast and ovarian cancers.
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