Transcriptome profile of the early stages of breast cancer tumoral spheroids
Por:
Pacheco-Marin, Rosario, Melendez-Zajgla, Jorge, Castillo-Rojas, Gonzalo, Mandujano-Tinoco, Edna, Garcia-Venzor, Alfredo, Uribe-Carvajal, Salvador, Cabrera-Orefice, Alfredo, Gonzalez-Torres, Carolina, Gaytan-Cervantes, Javier, Mitre-Aguilar, Irma B., Maldonado, Vilma
Publicada:
29 mar 2016
Categoría:
Multidisciplinary
Resumen:
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.
Filiaciones:
Natl Inst Genom Med, Epigenet, Periferico Sur 4809, Mexico City 14610, DF, Mexico
Univ Nacl Autonoma Mexico, Fac Med, Posgrad Program Biol Sci, Univ City Ave 3000, Mexico City 04510, DF, Mexico
Natl Inst Genom Med, Funct Genom Labs, Periferico Sur 4809, Mexico City 14610, DF, Mexico
Natl Autonomous Univ Mexico UNAM, Fac Med, Dept Microbiol & Parasitol, Microbial Mol Immunol Program, Univ City Ave 3000, Mexico City 04510, DF, Mexico
Univ Nacl Autonoma Mexico, Inst Cellular Physiol, Dept Mol Genet, Univ City Ave 3000, Mexico City 04510, DF, Mexico
Natl Inst Med Sci & Nutr Salvador Zubiran INCMNSZ, Unit Biochem, Av Vasco de Quiroga 15, Mexico City 14080, DF, Mexico
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