Figure 1: Schematic diagram of a stepwise omic-data integration which informs the in vivo therapeutic approach.
From: Local microRNA delivery targets Palladin and prevents metastatic breast cancer
Local miRNA delivery to the primary tumour is used to prevent breast cancer metastasis. To examine the effect of genomic alterations on breast cancer, we performed a stepwise omic-data integration to generate a narrow list of potentially functional variants for cancer metastasis, in which we intersect two datasets: TargetScan and dbSNP. Using this approach, we identified 20 SNPs, which are located at miRNA-binding sites in regulatory 3′-UTR regions of genes that are related to breast cancer (in particular those involved in cytoskeleton organization) (a). Our in vitro studies reveal miR-96 and miR-182 as key regulators of breast cancer cell motility via regulation of Palladin, which encodes a cytoskeletal protein that is required for organizing the actin cytoskeleton (b). Clinical data analysis supports clinical relevance in a human breast cancer cohort (c). Our data corroborate the role of miRNAs in metastasis regulation, and demonstrate that in vivo local delivery of miR-96 and miR-182 to the primary tumour can serve as a potential treatment to prevent breast cancer metastasis (d).
