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Biochem Biophys Res Commun. 2019 Sep 3;516(4):1258-1264. doi: 10.1016/j.bbrc.2019.06.155. Epub 2019 Jul 11.

Changes in the transcriptome profile of breast cancer cells grown as spheroids.

Author information

1
Laboratorio de Epigenética, CDMX, México; Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México (UNAM). CDMX, Mexico.
2
Genómica Functional. Instituto Nacional de Medicina Genómica (INMEGEN). CDMX, Mexico.
3
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México (UNAM), Estado de Mexico, Mexico.
4
Laboratorio de Epigenética, CDMX, México; Laboratorio de Tejido Conjuntivo. Instituto Nacional de Rehabilitación (INR) "Luis Guillermo Ibarra Ibarra". CDMX, Mexico.
5
Laboratorio de Epigenética, CDMX, México.
6
Laboratorio de Epigenética, CDMX, México. Electronic address: vmaldonado@inmegen.gob.mx.

Abstract

BACKGROUND:

Multicellular tumor spheroids mimic the functional organization of tumors in vivo, providing biological readouts that predict the behavior of cancer cells more accurately. The current study aimed to evaluate the transcriptome (mRNAs and long non-coding RNAs) of multicellular tumor spheroids from breast cancer cells.

METHODS:

MCF-7 cell spheroids were used; the transcriptome was analyzed using RNAseq and RNA microarrays; the secretion of macrophage migration inhibitor (MIF), a cytokine exported by the cholesterol efflux regulatory protein, was measured by ELISA. Linc00052 was inhibited using short-hairpin RNAs (shRNAs).

RESULTS:

We found several differentially regulated mRNAs and lncRNAs in MCF-7 cell spheroids. We also found significant enrichment of the Wnt/B-catenin death receptor and the cholesterol metabolic processes. Interestingly, we also found an increased concentration of MIF. Further, at 12 and 20 days of 3D culture we found 221 and 1146 dysregulated lncRNAs, respectively; including linc00052 (long intergenic non-protein coding RNA 52), which has been involved in breast cancer. Linc00052 knock-down experiments suggest that it could be a key regulator of cholesterol pathways in breast cancer.

CONCLUSIONS:

Our data shows that tumor spheroids can induce changes in the transcriptome of the cultured cells, including both mRNAs and ncRNA. One of the major changes included the deregulation of cholesterol pathways, of which linc00052 is apparently a key regulator.

KEYWORDS:

Breast cancer; Cholesterol; Long non-coding RNAs; MIF; Spheroid tumoral; linc00052

PMID:
31301772
DOI:
10.1016/j.bbrc.2019.06.155

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