A cross-platform comparison of affymetrix and Agilent microarrays reveals discordant miRNA expression in lung tumors of c-Raf transgenic mice

Non-coding RNAs play major roles in the translational control of gene expression. In order to identify disease-associated miRNAs in precursor lesions of lung cancer, RNA extracts from lungs of either c-Raf transgenic or wild-type (WT) mice were hybridized to the Agilent and Affymetrix miRNA microarr...

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Published in:	PloS one 2013-11, Vol.8 (11), p.e78870
Main Authors:	Del Vescovo, Valerio, Meier, Tatiana, Inga, Alberto, Denti, Michela Alessandra, Borlak, Juergen
Format:	Article
Language:	eng
Subjects:	3' Untranslated Regions Animal genetics Animals Base Pairing Base Sequence Biology Cancer Cell growth Cluster Analysis Comparative analysis Disease control DNA microarrays Dysplasia Female Gene expression Gene Expression Profiling - methods Gene Expression Regulation, Neoplastic Genes Genetic engineering Genomics House mouse Humans Hybridization Kinases Lesions Lung cancer Lung diseases Lung Neoplasms - genetics Lung Neoplasms - metabolism Lungs Male Mice Mice, Transgenic MicroRNA MicroRNAs MicroRNAs - genetics MicroRNAs - metabolism miRNA Mutation Pharmacology Platforms Proteins Proto-Oncogene Proteins c-raf - genetics Proto-Oncogene Proteins c-raf - metabolism Raf protein Reproducibility of Results Ribonucleic acid RNA RNA Interference Rodents Toxicology Transcription, Genetic Transgenic animals Transgenic mice Tumors
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Summary:	Non-coding RNAs play major roles in the translational control of gene expression. In order to identify disease-associated miRNAs in precursor lesions of lung cancer, RNA extracts from lungs of either c-Raf transgenic or wild-type (WT) mice were hybridized to the Agilent and Affymetrix miRNA microarray platforms, respectively. This resulted in the detection of a range of miRNAs varying between 111 and 267, depending on the presence or absence of the transgene, on the gender, and on the platform used. Importantly, when the two platforms were compared, only 11-16% of the 586 overlapping genes were commonly detected. With the Agilent microarray, seven miRNAs were identified as significantly regulated, of which three were selectively up-regulated in male transgenic mice. Much to our surprise, when the same samples were analyzed with the Affymetrix platform, only two miRNAs were identified as significantly regulated. Quantitative PCR performed with lung RNA extracts from WT and transgenic mice confirmed only partially the differential expression of significant regulated miRNAs and established that the Agilent platform failed to detect miR-433. Finally, bioinformatic analyses predicted a total of 152 mouse genes as targets of the regulated miRNAs of which 4 and 11 genes were significantly regulated at the mRNA level, respectively in laser micro-dissected lung dysplasia and lung adenocarcinomas of c-Raf transgenic mice. Furthermore, for many of the predicted mouse target genes expression of the coded protein was also repressed in human lung cancer when the publically available database of the Human Protein Atlas was analyzed, thus supporting the clinical significance of our findings. In conclusion, a significant difference in a cross-platform comparison was observed that will have important implications for research into miRNAs.
ISSN:	1932-6203 1932-6203