miRNA expression profile in multicellular breast cancer spheroids

摘要

Abstract Multicellular Tumor Spheroids develop a heterogeneous micromilieu and different cell populations, thereby constituting a cancer model with intermediate characteristics between in vitro bi-dimensional cultures and in vivo tumors. Multicellular Tumor Spheroids also acquire tumor aggressiveness features due to transcription modulation of coding and non-coding RNA. Utilizing microarray analyses, we evaluated the microRNAs expression profile in MCF-7 breast cancer cells cultured as Multicellular Tumor Spheroids. The expression data was used to predict associated cellular and molecular functions using different software tools. The biological importance of two dysregulated miRNAs (miR-221-3p and miR-187) was studied by functional assays. Finally, the clinical relevance of these dysregulated miRNAs was explored using previously reported data. Thirty-three dysregulated microRNAs were found in MCF-7 Multicellular Tumor Spheroids. miRNA expression changes were closely linked with growth, proliferation, and cell development. miRNA-221-3p and miR-187 were implicated in the acquisition of migration/invasion capacities, sensitivity to the deprivation of growth factors, cell cycle phase regulation, and cell death. A panel of 5 miRNAs, including miR-187, showed a good predictive value in discriminating between low and high-risk groups of breast cancer. Graphical abstract Display Omitted Highlights ? 33 microRNAs are differentially expressed in MCTS compared with monolayer culture. ? Proliferation, migration and invasion are regulated in MCTS by deregulated miRNAs. ? miR-221-3p and miR-187-3p have been associated with the B-Raf pathway. ? miR-221-3p and miR-187-3p regulate proliferation, migration and invasion of MCTS. ? miR-187 is able to discriminate between high and low risk groups of Breast Cancer patients. ]]>