PLX269833

GSE131876: The miR-146 family connects stem cell identity with cellular metabolism and pharmacological resistance in breast cancer

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Although ectopic overexpression of miRNAs can influence mammary normal and cancer stem cells (SCs/CSCs), their physiological relevance remains uncertain. Here, we found that the miR-146 family is linked to SC identity, since: i) their expression is very high in SCs/CSCs from human/mouse primary mammary tissues; correlates with the basal-like breast cancer subtype, which typically has a high CSC content; and specifically distinguishes cells with SC/CSC identity; ii) miR-146 depletion reduces SC/CSC self-renewal in vitro and the number of tumor-initiating cells in vivo. Analysis of the transcriptional effects of miR-146 in breast SC-like cells revealed a complex network of highly connected miR-146 targets related to quiescence, transcription and metabolic pathways (one-carbon pool, purine synthesis and folate metabolism). As predicted by our analysis, SCs/CSCs display innate resistance to anti-folate therapy that can be reversed by miR-146 depletion, unmasking a hidden vulnerability that could be exploited for the development of anti-CSC therapies. SOURCE: Francesco Nicassio (francesco.nicassio@iit.it) - Istituto Italiano di Tecnologia