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MiR-600 acts as a bimodal switcher that regulates breast cancer stem cell fate through WNT signaling


ABSTRACT: Breast cancer stem cells (bCSCs) have been implicated in tumor progression and therapeutic resistance; however, the molecular mechanisms that define bCSC-state are unclear. We have performed concurrent human miRNome-wide gain- and loss-of-function screens to identify switcher miRNAs controling the choice between bCSC self-renewal and differentiation. These analysis enlightened miR-600 whose silencing resulted in bCSC expansion. Mechanistically, miR-600 targets the stearoyl desaturase 1 (SCD1), an enzyme required to produce active, lipid-modified WNT proteins. To explore further miR-600 interactions and WNT-pathway, SUM159 cell line constructions were made and FACS-sorted to select the bCSCs. We compared gene expression profiles from native, miR-600 'over-expressed', miR-600'knock-down' and siSCD1 bCSCs. We showed that in the absence of miR-600, WNT signaling is maintained active and promotes self-renewal, whereas overexpression of miR-600 inhibits the production of active WNT proteins and promotes bCSC differentiation. These findings highlight a miR-600-centered signaling network that governs bCSC-fate decision and influences tumor progression.

SUBMITTER: Rita El Helou1 El Helou 

PROVIDER: E-MTAB-5393 | BioStudies | 2020-08-25

REPOSITORIES: biostudies

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