miRNome landscape analysis reveals a 30 miRNA core in retinoblastoma.

Autor: Castro-Magdonel BE; Medical Research Unit in Infectious Diseases, Hospital de Pediatría, CMN SXXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, 06720, Mexico City, Mexico.; Pharmacology Department, CINVESTAV, Mexico City, Mexico., Orjuela M; Epidemiology Department, Columbia University, New York, USA., Camacho J; Pharmacology Department, CINVESTAV, Mexico City, Mexico., García-Chéquer AJ; Medical Research Unit in Infectious Diseases, Hospital de Pediatría, CMN SXXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, 06720, Mexico City, Mexico., Cabrera-Muñoz L; Pathology Department, Hospital Infantil de México Federico Gómez, Secretaría de Salud, Mexico City, Mexico., Sadowinski-Pine S; Pathology Department, Hospital Infantil de México Federico Gómez, Secretaría de Salud, Mexico City, Mexico., Durán-Figueroa N; Unidad Profesional Interdisciplinaria de Biotecnología, Instituto Politécnico Nacional, Mexico City, Mexico., Orozco-Romero MJ; Unidad Profesional Interdisciplinaria de Biotecnología, Instituto Politécnico Nacional, Mexico City, Mexico., Velázquez-Wong AC; Medical Research Unit in Human Genetics, Hospital de Pediatría, CMN SXXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico., Hernández-Ángeles A; Medical Research Unit in Infectious Diseases, Hospital de Pediatría, CMN SXXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, 06720, Mexico City, Mexico., Hernández-Galván C; Ophthalmology Department, Hospital de Pediatría, CMN SXXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico., Lara-Molina C; Ophthalmology Department, Hospital Infantil de México Federico Gómez, Mexico City, Mexico., Ponce-Castañeda MV; Medical Research Unit in Infectious Diseases, Hospital de Pediatría, CMN SXXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, 06720, Mexico City, Mexico. vponce@ifc.unam.mx.
Jazyk: angličtina
Zdroj: BMC cancer [BMC Cancer] 2017 Jul 01; Vol. 17 (1), pp. 458. Date of Electronic Publication: 2017 Jul 01.
DOI: 10.1186/s12885-017-3421-3
Abstrakt: 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.
Databáze: MEDLINE
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