MiRNomics Reveals Breast Cancer Cells Cultured on 3D Scaffolds Better Mimic Tumors in Vivo than Conventional 2D Culture

Tissue-engineering-based
three-dimensional (3D) models offer several
advantages over conventional two-dimensional (2D) cultures and can
mimic tissues in vivo. Although studies have analyzed the changes
in the expression of genes and proteins that might mediate in vivo-like
signaling, the changes in the post-transcriptional control of gene
expression that are critical in fine-tuning of signaling events has
never been studied. In this study, we used next-generation sequencing
(NGS) to analyze the changes in the post-transcriptional regulation
in MDA-MB-231 breast cancer cells cultured on 3D scaffolds. The changes
in the expression of several known microRNAs were similar to the changes
reported in highly invasive cancers and their profiles highly correlated
with xenotumors and human breast tumors. To elucidate the role of
miRNAs in modulating metastatic potential, we integrated the miRNA
and the mRNA microarray data and developed networks for major pathways
implicated in metastasis. From these networks, we identified several
key miRNA-mRNA interactions that might contribute to the invasive
behavior and aid in developing a miRNA signature for highly invasive
breast cancers. This report on the differential regulation of miRNAs
in breast cancer cells cultured on scaffolds demonstrates that 3D
culture better mimics the tissue in vivo with novel insights into
the roles of miRNAs in modulating metastatic progression.