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CRISPR screens in 3D tumourspheres identified miR-4787-3p as a transcriptional start site miRNA essential for breast tumour-initiating cell growth.
- Source :
-
Communications Biology . 7/13/2024, Vol. 7 Issue 1, p1-11. 11p. - Publication Year :
- 2024
-
Abstract
- Our study employs pooled CRISPR screens, integrating 2D and 3D culture models, to identify miRNAs critical in Breast Cancer (BC) tumoursphere formation. These screens combine with RNA-seq experiments allowing identification of miRNA signatures and targets essential for tumoursphere growth. miR-4787-3p exhibits significant up-regulation in BC, particularly in basal-like BCs, suggesting its association with aggressive disease. Surprisingly, despite its location within the 5'UTR of a protein coding gene, which defines DROSHA-independent transcription start site (TSS)-miRNAs, we find it dependant on both DROSHA and DICER1 for maturation. Inhibition of miR-4787-3p hinders tumoursphere formation, highlighting its potential as a therapeutic target in BC. Our study proposes elevated miR-4787-3p expression as a potential prognostic biomarker for adverse outcomes in BC. We find that protein-coding genes positively selected in the CRISPR screens are enriched of miR-4787-3p targets. Of these targets, we select ARHGAP17, FOXO3A, and PDCD4 as known tumour suppressors in cancer and experimentally validate the interaction of miR-4787-3p with their 3'UTRs. Our work illuminates the molecular mechanisms underpinning miR-4787-3p's oncogenic role in BC. These findings advocate for clinical investigations targeting miR-4787-3p and underscore its prognostic significance, offering promising avenues for tailored therapeutic interventions and prognostic assessments in BC. A CRISPR/Cas9 genome wide screen in 2D breast cancer and 3D tumourspheres cultures identifies miR-4787-3p as a transcriptional tart site miRNA essential for breast tumour-initiating cell growth. [ABSTRACT FROM AUTHOR]
- Subjects :
- *BREAST
*CELL growth
*CRISPRS
*MEDICAL screening
*MICRORNA
*GENETIC code
Subjects
Details
- Language :
- English
- ISSN :
- 23993642
- Volume :
- 7
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Communications Biology
- Publication Type :
- Academic Journal
- Accession number :
- 178416450
- Full Text :
- https://doi.org/10.1038/s42003-024-06555-1