MicroRNA Expression Aberration Associated with Bronchopulmonary Dysplasia in Preterm Infants: A Preliminary Study

Abstract

BACKGROUND:

Because environmental insults and genetic factors account for the variance in the risk of bronchopulmonary dysplasia (BPD) in very low birth weight (VLBW, birth weight < 1,500 g) preterm infants, the search for BPD biomarkers has begun to focus on the regulators of non-coding RNA such as microRNAs (miRNAs). Therefore, this study aimed to identify potential miRNAs involved in the pathogenesis of BPD in VLBW preterm infants.

METHODS:

A case-control study (15 subjects with BPD and 15 sex-matched control subjects without BPD) was conducted to investigate the expression profiles of 365 miRNAs in the peripheral blood of VLBW preterm infants at 36 weeks post-menstrual age (called the older-age set). The expression levels of identified miRNAs were further evaluated in a subsample of blood collected during the first 2 weeks post-natal age (called the younger-age set). Possible biological functions and pathways implicated in the target genes regulated by the miRNAs were explored using database predictions.

RESULTS:

A 4-miRNA signature (miR-152, miR-30a-3p, miR-133b, and miR-7) with aberrant expression levels at 36 weeks, derived from a supervised classification with internal cross-validation, discriminated the subjects with BPD from those without BPD with an accuracy of 0.91. The discriminative accuracy of the 4 miRNAs was supported by random permutations of either the disease status or the number of miRNAs selected (both P < .001). A down-regulation change of miR-152 and miR-30a-3p expression levels and an up-regulation change of miR-133b and miR-7 expression levels were found in the older-age set, compared to the younger-age set.

CONCLUSIONS:

This is the first study to identify blood-based miRNAs associated with BPD. The findings provide information regarding the roles of these biomarkers in the development of BPD in VLBW preterm infants.