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Biochim Biophys Acta Mol Cell Res. 2017 Oct;1864(10):1642-1655. doi: 10.1016/j.bbamcr.2017.05.023. Epub 2017 May 31.

miRNA expression profile in multicellular breast cancer spheroids.

Author information

1
Epigenetic Laboratory, Instituto Nacional de Medicina, Genómica, Periférico Sur 4809, Arenal Tepepan, 14610 Ciudad de Mexico, Mexico; Facultad de Medicina, Universidad Nacional Autónoma de México, Avenida Universidad 3000, Coyoacán, 04510 Ciudad de Mexico, Mexico.
2
Epigenetic Laboratory, Instituto Nacional de Medicina, Genómica, Periférico Sur 4809, Arenal Tepepan, 14610 Ciudad de Mexico, Mexico.
3
Laboratory of Connective Tissue, Centro Nacional de Investigación y Atención de Quemados, Instituto Nacional de Rehabilitación, Ciudad de Mexico, Mexico.
4
Functional Genomics Laboratory, Instituto Nacional de Medicina, Genómica, Periférico Sur 4809, Arenal Tepepan, 14610 Ciudad de Mexico, Mexico.
5
Epigenetic Laboratory, Instituto Nacional de Medicina, Genómica, Periférico Sur 4809, Arenal Tepepan, 14610 Ciudad de Mexico, Mexico. Electronic address: vmaldonado@inmegen.gob.mx.

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.

KEYWORDS:

Breast cancer; Multicellular tumor spheroid; miRNAs; mir-187; mir-221

PMID:
28576513
DOI:
10.1016/j.bbamcr.2017.05.023
[Indexed for MEDLINE]
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