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BMC Cancer
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

miRNome landscape analysis reveals a 30 miRNA core in retinoblastoma

Authors: Blanca Elena Castro-Magdonel, Manuela Orjuela, Javier Camacho, Adda Jeanette García-Chéquer, Lourdes Cabrera-Muñoz, Stanislaw Sadowinski-Pine, Noé Durán-Figueroa, María de Jesús Orozco-Romero, Ana Claudia Velázquez-Wong, Adriana Hernández-Ángeles, Claudia Hernández-Galván, Citlali Lara-Molina, M. Verónica Ponce-Castañeda

Published in: BMC Cancer | Issue 1/2017

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Abstract

Background

miRNAs exert their effect through a negative regulatory mechanism silencing expression upon hybridizing to their target mRNA, and have a prominent position in the control of many cellular processes including carcinogenesis. Previous miRNA studies on retinoblastoma (Rb) have been limited to specific miRNAs reported in other tumors or to medium density arrays. Here we report expression analysis of the whole miRNome on 12 retinoblastoma tumor samples using a high throughput microarray platform including 2578 mature miRNAs.

Methods

Twelve retinoblastoma tumor samples were analyzed using an Affymetrix platform including 2578 mature miRNAs. We applied RMA analysis to normalize raw data, obtained categorical data from detection call values, and also used signal intensity derived expression data. We used Diana-Tools-microT-CDS to find miRNA targets and ChromDraw to map miRNAs in chromosomes.

Results

We discovered a core-cluster of 30 miRNAs that were highly expressed in all the cases and a cluster of 993 miRNAs that were uniformly absent in all cases. Another 1022 miRNA were variably present in the samples reflecting heterogeneity between tumors. We explored mRNA targets, pathways and biological processes affected by some of these miRNAs. We propose that the core-cluster of 30 miRs represent miRNA machinery common to all Rb, and affecting most pathways considered hallmarks of cancer. In this core, we identified miR-3613 as a potential and critical down regulatory hub, because it is highly expressed in all the samples and its potential mRNA targets include at least 36 tumor suppressor genes, including RB1. In the variably expressed miRNA, 36 were differentially expressed between males and females. Some of the potential pathways targeted by these 36 miRNAs were associated with hormonal production.

Conclusion

These findings indicate that Rb tumor samples share a common miRNA expression profile regardless of tumor heterogeneity, and shed light on potential novel therapeutic targets such as mir-3613 This is the first work to delineate the miRNA landscape in retinoblastoma tumor samples using an unbiased approach.
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Metadata
Title
miRNome landscape analysis reveals a 30 miRNA core in retinoblastoma
Authors
Blanca Elena Castro-Magdonel
Manuela Orjuela
Javier Camacho
Adda Jeanette García-Chéquer
Lourdes Cabrera-Muñoz
Stanislaw Sadowinski-Pine
Noé Durán-Figueroa
María de Jesús Orozco-Romero
Ana Claudia Velázquez-Wong
Adriana Hernández-Ángeles
Claudia Hernández-Galván
Citlali Lara-Molina
M. Verónica Ponce-Castañeda
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3421-3

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