Abstract

Plasma microRNAs (miRNAs) have recently emerged as a new class of regulatory molecules that influence many biological functions. However, the expression profile of plasma microRNAs in nonsyndromic cleft palate (NSCP) or nonsyndromic cleft lip with cleft palate (NSCLP) remains poorly investigated. In this study, we used Agilent human miRNA microarray chips to monitor miRNA levels in three NSCP plasma samples (mixed as the CP group), three NSCLP plasma samples (mixed as the CLP group) and three normal plasma samples (mixed as the Control group). Six selected plasma miRNAs were validated in samples from an additional 16 CP, 33 CLP and 8 healthy children using qRT-PCR. Using Venn diagrams, distinct and overlapping dysregulated miRNAs were identified. Their respective target genes were further assessed using gene ontology and pathway analysis. The results show that distinct or overlapping biological processes and signalling pathways were involved in CP and CLP. Our study showed that the common key gene targets reflected functional relationships to the Notch, Wnt, phosphatidylinositol and Hedgehog signalling pathways. Further studies should examine the mechanism of the potential target genes, which may provide new avenues for future clinical prevention and therapy.

Highlights

  • Orofacial clefts include cleft palate only (CPO), cleft lip with cleft palate (CLP) and cleft lip only (CLO)

  • To investigate whether circulating miRNAs are associated with the pathogenesis of cleft palate and cleft lip with cleft palate, plasma samples were collected from healthy children and children with nonsyndromic cleft palate (NSCLP) and cleft lip with cleft palate (NSCLP)

  • A comprehensive miRNA microarray analysis was performed on nine plasma samples, including three nonsyndromic cleft palate (NSCP) plasma samples, three nonsyndromic cleft lip with cleft palate (NSCLP) plasma samples and three plasma samples from healthy children

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Summary

Introduction

Orofacial clefts include cleft palate only (CPO), cleft lip with cleft palate (CLP) and cleft lip only (CLO). 1/800 live births worldwide are affected by these diseases [1]. Nonsyndromic orofacial clefts occur as isolated entities with no other apparent structural and/or developmental abnormalities. The majority of CLP cases are nonsyndromic (NS) (~70%) [2]. Cleft palate only (CPO) is the least common form of the orofacial clefts (approximately 33%) [3]. The aetiology is multifactorial and involves both genetic and environmental risk factors. Most studies suggest that distinct etiological mechanisms underlie CLP and CPO [4, 5]; some overlapping exists in their aetiologies [6, 7]. Our knowledge about whether CPO does differ from CLP remains incomplete

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