Abstract Objective To study the continuous expression and potential function of circular RNA (circRNA), circ4:150439343|150477468 and circ15:73330849|73343359, in mouse lung development. Methods According to the stage of lung development, lung tissue samples were collected from mice on embryonic day 16.5 (E16.5), embryonic day 18.5 (E18.5), and postnatal day 2 (P2). Hematoxylin and eosin staining was performed to observe the morphology of lung tissue. Quantitative real-time PCR (qRT-PCR) was used to measure the mRNA expression of circ4:150439343|150477468 and circ15:73330849|73343359 during late lung development; miRanda and TargetScan were used to predict the target miRNAs of circRNAs, and then GO and KEGG analysis was performed for the target genes to predict the potential function of circRNAs. Results Type Ⅱ alveolar epithelial cells were observed in the lung slices of E16.5 mice, with a gradual increase in number. On P2, the pulmonary alveoli expanded rapidly, the pulmonary interstitium became thinner, and the alveolar structure gradually became mature. The results of qRT-PCR showed that the relative expression of circ4:150439343|150477468 was continuously upregulated over time and the relative expression of circ15:73330849|73343359 was first downregulated and then upregulated (P < 0.05). The KEGG and GO analysis showed that circRNAs were involved in the Notch, PI3K-Akt, and NF-κB signaling pathways. Conclusions Circ4:150439343|150477468 and circ15:73330849|73343359 can participate in lung development through the Notch signaling pathway.
FU Xue,YANG Yang,SHEN Yan-Qing et al. Continuous expression and functional prediction of circular RNA in mouse lung development[J]. CJCP, 2020, 22(10): 1125-1130.
FU Xue,YANG Yang,SHEN Yan-Qing et al. Continuous expression and functional prediction of circular RNA in mouse lung development[J]. CJCP, 2020, 22(10): 1125-1130.
Revhaug C, Bik-Multanowski M, Zasada M, et al. Immune system regulation affected by a murine experimental model of bronchopulmonary dysplasia:genomic and epigenetic findings[J]. Neonatology, 2019, 116(3):269-277.
[2]
Baker CD. Long-term ventilation for children with chronic lung disease of infancy[J]. Curr Opin Pediatr, 2019, 31(3):357-366.
[3]
Kristensen LS, Andersen MS, Stagsted LVW, et al. The biogenesis, biology and characterization of circular RNAs[J]. Nat Rev Genet, 2019, 20(11):675-691.
[4]
Du WW, Zhang C, Yang W, et al. Identifying and characterizing circRNA-protein interaction[J]. Theranostics, 2017, 7(17):4183-4191.
[5]
Rong D, Sun H, Li Z, et al. An emerging function of circRNA-miRNAs-mRNA axis in human diseases[J]. Oncotarget, 2017, 8(42):73271-73281.
[6]
Sun P, Li G. CircCode:a powerful tool for identifying circRNA coding ability[J]. Front Genet, 2019, 10:981.
[7]
Zhang G, Diao S, Zhang T, et al. Identification and characterization of circular RNAs during the sea buckthorn fruit development[J]. RNA Biol, 2019, 16(3):354-361.
[8]
Hu X, Zhu M, Liu B, et al. Circular RNA alterations in the Bombyx mori midgut following B. mori nucleopolyhedrovirus infection[J]. Mol Immunol, 2018, 101:461-470.
[9]
Shen YQ, Pan JJ, Sun ZY, et al. Differential expression of circRNAs during rat lung development[J]. Int J Mol Med, 2019, 44(4):1399-1413.
[10]
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method[J]. Methods, 2001, 25(4):402-408.
[11]
Langmead B, Trapnell C, Pop M, et al. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome[J]. Genome Biol, 2009, 10(3):R25.
[12]
Morty RE. Recent advances in the pathogenesis of BPD[J]. Semin Perinatol, 2018, 42(7):404-412.
[13]
Wu CX, Cheng J, Wang YY, et al. Microrna expression profiling of macrophage line raw264.7 infected by candida albicans[J]. Shock, 2017, 47(4):520-530.
[14]
Kiyokawa H, Morimoto M. Notch signaling in the mammalian respiratory system, specifically the trachea and lungs, in development, homeostasis, regeneration, and disease[J]. Dev Growth Differ, 2020, 62(1):67-79.
[15]
Espín-Palazón R, Traver D. The NF-κB family:key players during embryonic development and HSC emergence[J]. Exp Hematol, 2016, 44(7):519-527.
[16]
Liu J, Sato C, Cerletti M, et al. Notch signaling in the regulation of stem cell self-renewal and differentiation[J]. Curr Top Dev Biol, 2010, 92(10):367-409.
[17]
Hussain M, Xu C, Ahmad M, et al. Notch signaling:linking embryonic lung development and asthmatic airway remodeling[J]. Mol Pharmacol, 2017, 92(6):676-693.
[18]
Taichman DB, Loomes KM, Schachtner SK, et al. Notch1 and jagged1 expression by the developing pulmonary vasculature[J]. Dev Dyn, 2002, 225(2):166-175.
[19]
Liu Y, Sadikot RT, Adami GR, et al. FoxM1 mediates the progenitor function of typeⅡepithelial cells in repairing alveolar injury induced by Pseudomonas aeruginosa[J]. J Exp Med, 2011, 208(7):1473-1484.
[20]
Xu K, Nieuwenhuis E, Cohen BL, et al. Lunatic fringe-mediated notch signaling is required for lung alveogenesis[J]. Am J Physiol Lung Cell Mol Physiol, 2010, 298(1):L45-L56.
[21]
Tsao PN, Matsuoka C, Wei SC, et al. Epithelial notch signaling regulates lung alveolar morphogenesis and airway epithelial integrity[J]. Proc Natl Acad Sci U S A, 2016, 113(29):8242-8247.