Abstract
Bronchopulmonary dysplasia (BPD) is characterized by impaired vascular and alveolar development, and the underlying molecular mechanisms have remained elusive. MicroRNAs are important players in various biological functions including the pathogenesis of BPD. The present study aimed to examine the expression of miR-203a-3p in the peripheral blood of BPD patients and elucidate the mechanisms underlying miR-203a-3p-mediated progression of BPD. We examined the expression of miR-203a-3p in the peripheral blood of BPD patients and found that miR-203a-3p was up-regulated in the patients. Additionally, the mRNA expression levels of vascular endothelial growth factor A (VEGFA) and hypoxia-inducible factor-1alpha were down-regulated in the BPD patients. Further in vitro studies showed that miR-203a-3p suppressed the expression of VEGFA in RLE-6TN cells by targeting the VEGFA 3′ untranslated region. Overexpression of miR-203a-3p inhibited the viability of RLE-6TN cells and induced cell apoptosis, whereas the knockdown of miR-203a-3p exerted opposite effects. VEGFA treatment significantly attenuated the increase in the RLE-6TN cell apoptotic rates induced by miR-203a-3p overexpression; while VEGFA knockdown significantly increased the cell apoptotic rates of RLE-6TN cells, which was partially reversed by the treatment with miR-203a-3p inhibitor. Furthermore, miR-203a-3p was up-regulated, whereas VEGFA was down-regulated in the lung tissues of BPD rats, and sequestration of the expression of miR-203a-3p prevented hyperoxia-induced lung damage, increased VEGFA mRNA and protein expression levels, and promoted the protein expression of ERK, PI3K, and p38 in the lung tissues of BDP rats. In summary, the findings of our study indicate that miR-203a-3p knockdown alleviates hyperoxia-induced lung tissue damage in the BPD rat model, and its effect may be associated with the up-regulation of VEGF.
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All the data generated in this study are available upon reasonable request from the corresponding author.
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BW and DL conceived the study; LC and YW performed the data analysis and the experiments; TH edited the manuscript. All the authors approved the manuscript for submission.
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The study was approved by the Ethics Committee of Shenzhen People’s Hospital. Human blood samples were obtained from these patients and written informed consent was obtained from the guardians of the patients.
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Supplemental Figure S1
MiR-203a-3p was regulated by HIF-1α signaling in RLE-6TN cells. (A) TargetScan analysis of the predicted binding sites between miR-203a-3p and HIF-1α 3’UTR. (B and C) qRT-PCR analysis of HIF-1α expression in RLE-6TN cells after being transfected with mimics-NC, miR-203a-3p mimics, inhibitor NC or miR-203a-3p inhibitor. (D) qRT-PCR analysis of miR-203a-3p expression in RLE-6TN cells after being treated with HIF-1α activator (DMOG). N = 3. *P < 0.05. (PNG 5473 kb)
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Cheng, H., Chen, L., Wei, Y. et al. Knockdown of miR-203a-3p alleviates the development of bronchopulmonary dysplasia partly via the up-regulation of vascular endothelial growth factor A. J Bioenerg Biomembr 53, 13–23 (2021). https://doi.org/10.1007/s10863-020-09863-3
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DOI: https://doi.org/10.1007/s10863-020-09863-3