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Sci Rep. 2016 Mar 29;6:23373. doi: 10.1038/srep23373.

Transcriptome profile of the early stages of breast cancer tumoral spheroids.

Author information

1
Epigenetics, National Institute of Genomic Medicine, Periférico Sur No. 4809, Col Arenal Tepepan, Delegación Tlalpan, México, D.F., C.P 14610.
2
Posgraduate Program in Biological Sciences, Faculty of Medicine (UNAM), University City Avenue 3000 C.P. 04510, Coyoacan, Mexico City.
3
Functional Genomics laboratories, National Institute of Genomic Medicine, Periférico Sur No. 4809, Col Arenal Tepepan, Delegación Tlalpan, México, D.F., C.P 14610.
4
Microbial Molecular Immunology Program, Department of Microbiology and Parasitology, Faculty of Medicine, National Autonomous University of Mexico (UNAM), University City Avenue 3000 C.P. 04510, Coyoacan, Mexico City.
5
Department of Molecular Genetics, Institute of Cellular Physiology (UNAM), University City Avenue 3000 C.P. 04510, Coyoacan, Mexico City.
6
Unit of Biochemistry, National Institute of Medical Sciences and Nutrition Salvador Zubirán (INCMNSZ), Av. Vasco de Quiroga N° 15, Colonia Belisario Domínguez Sección XVI, Delegación Tlalpan. CP.14080, México D. F., México.

Abstract

Oxygen or nutrient deprivation of early stage tumoral spheroids can be used to reliably mimic the initial growth of primary and metastatic cancer cells. However, cancer cell growth during the initial stages has not been fully explored using a genome-wide approach. Thus, in the present study, we investigated the transcriptome of breast cancer cells during the initial stages of tumoral growth using RNAseq in a model of Multicellular Tumor Spheroids (MTS). Network analyses showed that a metastatic signature was enriched as several adhesion molecules were deregulated, including EPCAM, E-cadherin, integrins and syndecans, which were further supported by an increase in cell migration. Interestingly, we also found that the cancer cells at this stage of growth exhibited a paradoxical hyperactivation of oxidative mitochondrial metabolism. In addition, we found a large number of regulated (long non coding RNA) lncRNAs, several of which were co-regulated with neighboring genes. The regulatory role of some of these lncRNAs on mRNA expression was demonstrated with gain of function assays. This is the first report of an early-stage MTS transcriptome, which not only reveals a complex expression landscape, but points toward an important contribution of long non-coding RNAs in the final phenotype of three-dimensional cellular models.

PMID:
27021602
PMCID:
PMC4810430
DOI:
10.1038/srep23373
[Indexed for MEDLINE]
Free PMC Article

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