1. INTRODUCTION
Bronchopulmonary dysplasia (BPD) is one of the common chronic lung
diseases in preterm infants, and its incidence is as high as 52% in
extremely low birth weight infants 1, 2. With the
increasing maturity of critical care and management techniques for
premature infants, the survival rate of very low and extremely low birth
weight infants has increased significantly, but with it, the incidence
of BPD has also shown a continuous upward trend 3.
Children with this disease not only suffer from repeated respiratory
infections and varying degrees of pulmonary dysfunction, but also
increase the risk of asthma and chronic obstructive pulmonary disease
(COPD) in adulthood 4. Therefore, BPD has become an
important medical problem that endangers the health of newborns, affects
the quality of our nationals, and causes a heavy family and
socioeconomic burden.
LncRNAs are a type of non-coding transcript that is greater than 200
nucleotides in length and does not have the ability to encode proteins.
In recent years, with the rapid development of genetic information
technology and the wide application of next-generation sequencing and
gene chip technology, scholars’ understanding of the pathogenesis of
many human diseases has gradually expanded to the level of lncRNA and
has become a research hotspot in many fields of life medicine. It has
also become a new direction for us to explore the pathogenesis of BPD.
LncRNAs have abundant biological functions in cell development and
metabolism, such as genetic imprinting 5, chromatin
modification 6, cell cycle regulation7, transcription regulation 8, and
participation in mRNA degradation 9 Etc. These are
closely related to the occurrence, development and prevention of many
human diseases. Studies on the role and mechanism of lncRNA in lung
development and lung diseases have become a hot spot of increasing
attention by scholars. Herriges MJ et al. 10identified 363 lncRNAs in embryonic mouse lungs, which interact with
transcription factors spatially to regulate lung development. The lack
of certain lncRNAs in the lungs can lead to alveolar capillary dysplasia
and pulmonary vein dislocation (ACD/MPV) 11. Studies
have also confirmed that lncRNA plays the role of ”inducers and
terminators” of vascular development 12, affects the
biological functions of endothelial cells, and can be used as a target
for vascular diseases 13. Although there have been
preliminary studies of lncRNA in the field of lung development, further
exploration of the role and mechanism of lncRNA in the formation of BPD
will inevitably promote neonatal scholars’ in-depth understanding of the
pathogenesis of BPD.
In this study, we identified a molecular effector mechanism of the
lncRNA uc.375 in lung tissue of BPD using lncRNA microarray,
bioinformatics, and functional studies. We found that uc.375 is mainly
distributed in AEC II, and low expression in BPD mice AEC II. Silencing
uc.375 promoted the apoptosis of MLE 12 cells, reduced their
proliferation and differentiation, and promoted the apoptosis-related
factor caspase 3, inhibited the expression of MLE 12 specific secretion
SP-C, bcl2 and UCP2. On the contrary, after overexpressing uc.375, the
opposite results were obtained. Silencing uc.375 while silencing FoxA1
inhibited MLE 12 apoptosis, promoted their proliferation, inhibited
apoptosis-related factor caspase3, and promoted the expression of MLE
12-specific secretions SP-C , bcl2 and UCP2. On the contrary,
overexpression of uc.375 and FoxA1 at the same time, the result is
opposite. uc.375 negatively regulates FoxA1 expression, affects alveolar
development, and plays an important role in the occurrence and
development of BPD. In summary, this study clarified the exact mechanism
of uc.375 in the occurrence and development of BPD. we identified that it
may provide a new molecular target for the prevention and treatment of
BPD.