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.