Microarray expression profiling of dysregulated long non-coding RNAs in Hirschsprung's disease reveals their potential role in molecular diagnosis

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Abstract

Background

Hirschsprung's disease (HSCR) is one of the common digestive disorders in the new born. Long non-coding RNAs (lncRNAs) play an important role in various biological processes. However, knowledge on lncRNAs in HSCR is limited.

Methods

The expression profile of lncRNAs in HSCR was obtained using microarray. A total of 2078 differentially expressed lncRNAs were detected by microarray in HSCR tissues compared with matched normal colon tissues (fold change ≥2, p < 0.05). Candidate biomarkers were selected from these differentially expressed lncRNAs based on artificial criterion (raw signal intensity ≥50; fold change ≥8) and then validated in 80 pairs of HSCR and normal tissues using quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, the computational analysis was used to evaluate the lncRNA-microRNA and lncRNA–protein relationships.

Key Results

A panel of 5-lncRNAs was identified to distinguish HSCR from normal tissues with remarkable sensitivity and specificity. The area under the receiver operating characteristic curve (AUC) for HSCR identification in the validation set was 0.875. The bioinformatics analysis reveals that these dysregulated lncRNAs are mainly involved in RNA–protein relationships, including RNA splicing, binding, transport, processing, and localization.

Conclusions & Inferences

Our results are the first to report the expression profile of dysregulated lncRNAs in HSCR and infer that lncRNAs may serve as novel diagnostic biomarkers for HSCR.

A total of 2078 differently expressed lncRNAs were detected in HSCR tissues compared with normal gut tissues. A panel of 5-lncRNAs serving as candidate biomarkers was selected from these dysregulated lncRNAs based on artificial criterion and then validated in 80 pairs of HSCR and normal tissues. The computational analysis revealed the five selected lncRNAs are mainly involved in RNA–protein relationships including RNA splicing, binding, transport, processing, and localization.

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