MiR-342 suppression of an E2F signaling network limits metastatic outgrowth of triple negative breast cancer [RNA-Seq]

Through integrated analysis of metastatic TNBC mouse models and patient datasets, we identified miR-342 as a clinically relevant suppressor of TNBC metastasis. Ectopic expression of miR-342 was sufficient to repress TNBC metastasis in immune competent and xenograft mouse models, specifically limiting the outgrowth of disseminated tumour cells.

Using a multi-omics approach, including Argonaute-HITS-CLIP, we identified the global complement of miR-342 targets in TNBC. Through targeting of E2F1 and many downstream E2F target genes, miR-342 orchestrates both transcriptional and post-transcriptional regulatory networks that converge to suppress E2F signalling in TNBC. Consistent with this, inhibition of the E2F pathway with the CDK4/6 inhibitor palbociclib reduces metastatic outgrowth of TNBC.