1.Introduction
Nowadays, with the development of the department of neonatology and advancements in medical technology, the number of premature infants surviving the neonatal period has been increasing. However, this has been accompanied by an increasing number of cases of bronchopulmonary dysplasia (BPD) in preterm infants (Jobe, 2011), a chronic lung disease with significant morbidity and mortality mainly due to long time oxygen therapy during the late canalicular or saccular phases of lung development. Accordingly, this might cause long term consequences in the neonates. Researches have shown that infants with BPD are easier to get respiratory infections and are more susceptible to frequent hospitalizations compared with healthy preterm and term infants in the first 2 y of their life (Hilgendorff and O’Reilly, 2015). The pathogenesis of BPD has not been well elucidated yet, so identifying the mechanism that leads to the occurrence and development of BPD is an important issue.
The diagnostic criteria of BPD changes over time. The National Institute of Child Health and Human Development (NICHD) guidelines in 2001 imposed that the diagnose of BPD requires accumulated oxygen inhalation for at least 28 days after birth. While new NICHD guidelines in 2018 imposed that the diagnose of BPD should according to the oxygen concentration for at least 3 consecutive days at 36 weeks post-menstrual age (PMA). There is no question that BPD is a complex disease that develops progressively, has multiple causes, has a spectrum of severity and the diagnosis is relatively nonspecific which can differ between regions.
In recent years, the genetic background has been involved in the pathogenesis of BPD (Wang et al., 2019). Nowadays, we can disclose the molecular mechanism of BPD using high-throughput sequencing and high‐resolution microarray analysis. Microarray analysis is a high-throughput, high-efficiency, and high-automation method that has been widely used in scientific research to provide the expression level of messenger RNA (mRNA) and noncoding RNAs (ncRNAs) in samples (Hung and Weng, 2017; Bolón-Canedo et al., 2019). Noted, ncRNAs mainly includes microRNA (miRNA), circular RNA (circRNA), and long noncoding RNA (lncRNA). Accordingly, miRNAs is a group of highly stable single-stranded RNA molecules that have been reported to play important roles in post-transcriptional gene regulation (Yang et al., 2013). They have been shown to regulate the mRNA and protein expression in various physiological and pathological processes, such as cellular differentiation, proliferation, apoptosis, angiogenesis, and cancer development (Hatley et al., 2010).
Many studies have revealed the role of miRNA during the pathogenesis of BPD (Silva et al., 2015).These miRNAs have been shown to regulate their targeted downstream genes through changes (over- or under-) in their expression. Lal et al. found that under-expression of miR-876-3p was connected with the development of BPD (Lal et al., 2018), Whereas, Zhang et al. found that over-expression of miRNA-206 contributed to the development of BPD through the up-regulation of fibronectin 1 (Zhang et al., 2013). However, despite ongoing research in this field, the molecular mechanism of BPD remains poorly understood. As far as we know, there have been few studies using microarray datasets to obtain key genes and construct miRNA-mRNA regulatory pathways in BPD. Our study aimed to identify the key genes and differentially expressed miRNA (DEMs) and their underlying regulatory mechanisms in BPD using bioinformatic methods.