MicroRNA expression profiling and target genes study in congenital microtia

ObjectiveMicrotia is a complicated congenital anomaly with a genetic and environmental predisposition, and the molecular events underlying this disease are not fully understood. MicroRNAs (miRNAs) are a class of 20-22 nucleotide non-coding RNAs that function to control post-transcriptional gene expression. We want to find the miRNA expression profiling of microtia by using Affymetrix GeneChip® miRNA 2.0 Arrays.MethodsWe selected 9 microtia cartilages and 3 normal controls for GeneChip® miRNA 2.0 Arrays analysis. The altered miRNA were analyzed by poly (A) RT-PCR from 58 microtia samples and 16 normal controls. We predicted the target genes of miRNAs by bioinformatics and RT-PCT was used to confirm the target genes.ResultsWe found 11 miRNAs with significantly altered expression in the microtic group compared to the normal controls, which included 6 up-regulated miRNAs and 5 down-regulated miRNAs. These miRNAs were further examined using poly (A) RT-PCR analysis, we found that miR-451 and miR-486-5p were significantly up-regulated and miR-200c was significantly down-regulated in the microtic group compared to the normal controls (p < 0.05). Several complementary target messenger RNAs (mRNAs) had been predicted. OSR1, the target gene of miR-451 and miR-200c, was significantly up-regulated (p < 0.01); TRPS1, the target gene of miR-200c, was significantly down-regulated in the microtic group compared to the controls (p < 0.0001).ConclusionThe reduction in miR-200c expression and the accretion of miR-451 and miR-486-5p expression in microtic samples could be possible causes of the abnormal development of the external ear. OSR1 and TRPS1, as the complementary target mRNAs, may play important roles during the development of the external ear. Further studies are still needed to identify the miRNA target genes and to determine their function in the pathogenesis of microtia. This is the first report of a relationship between miRNAs and microtia.