MicroRNA expression profiles and target prediction in neonatal Wistar rat lungs during the development of bronchopulmonary dysplasia

Xing,Yujiao; Fu,Jianhua; Yang,Haiping; Yao,Li; Qiao,Lin; Du,Yanna; Xue,Xindong

doi:10.3892/ijmm.2015.2347

MicroRNA expression profiles and target prediction in neonatal Wistar rat lungs during the development of bronchopulmonary dysplasia

Authors:
- Yujiao Xing
- Jianhua Fu
- Haiping Yang
- Li Yao
- Lin Qiao
- Yanna Du
- Xindong Xue
View Affiliations

Affiliations: Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
Published online on: September 17, 2015 https://doi.org/10.3892/ijmm.2015.2347
Pages: 1253-1263
Copyright: © Xing et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

In this study, we investigated the mechanisms through which microRNAs (miRNAs or miRs) regulate lung development after birth, as well as the role of miRNAs in the development of bronchopulmonary dysplasia (BPD). For this purpose, a total of 90 neonatal Wistar rats were randomly and equally assigned to either a model group or a control group. On postnatal days 3, 7 and 14, the lung tissues were collected for histological analysis to determine morphological changes. The expression levels of proliferating cell nuclear antigen (PCNA) and platelet endothelial cell adhesion molecule-1 (PECAM-1, also known as CD31) were measured by RT-qPCR and western blot analysis. A miRCURY™ LNA array was employed to screen for differentially expressed miRNAs, and the possible target genes of those miRNAs were predicted. Our results revealed that, compared with the control group, the following changes induced by hyperoxia were observed in the model group over time: a decrease in the number, but an increase in the size of the alveoli, and a decrease in the number of secondary septa formed. In the model group, from postnatal days 3-14, the mRNA and protein expression levels of PCNA and CD31 were significantly lower than those in the control group. The differentially expressed miRNAs between the 2 groups were identified on days 3, 7 and 14 after birth. Possible target genes were identified for 32 differentially expressed miRNAs. Taken together, these findings suggest that during the development of BPD, an alveolarization disorder with microvascular dysplasia co-exists with the differential expression of certain miRNAs during the different stages of alveolar development in a neonatal rat model of hyperoxia‑induced BPD. This indicates that miRNAs may participate in the occurrence and development of BPD.

View Figures

View References

1	Hilgendorff A, Reiss I, Ehrhardt H, Eickelberg O and Alvira CM: Chronic lung disease in the preterm infant. Lessons learned from animal models. Am J Respir Cell Mol Biol. 50:233–245. 2014.
2	Bhandari A and Bhandari V: Pitfalls, problems, and progress in bronchopulmonary dysplasia. Pediatrics. 123:1562–1573. 2009. View Article : Google Scholar : PubMed/NCBI
3	Bhandari A and McGrath-Morrow S: Long-term pulmonary outcomes of patients with bronchopulmonary dysplasia. Semin Perinatol. 37:132–137. 2013. View Article : Google Scholar : PubMed/NCBI
4	Anderson PJ and Doyle LW: Neurodevelopmental outcome of bronchopulmonary dysplasia. Semin Perinatol. 30:227–232. 2006. View Article : Google Scholar : PubMed/NCBI
5	Herriges M and Morrisey EE: Lung development: orchestrating the generation and regeneration of a complex organ. Development. 141:502–513. 2014. View Article : Google Scholar : PubMed/NCBI
6	Warburton D, El-Hashash A, Carraro G, Tiozzo C, Sala F, Rogers O, De Langhe S, Kemp PJ, Riccardi D, Torday J, et al: Lung organogenesis. Curr Top Dev Biol. 90:73–158. 2010. View Article : Google Scholar : PubMed/NCBI
7	Hadchouel A, Franco-Montoya ML and Delacourt C: Altered lung development in bronchopulmonary dysplasia. Birth Defects Res A Clin Mol Teratol. 100:158–167. 2014. View Article : Google Scholar : PubMed/NCBI
8	Madurga A, Mizíková I, Ruiz-Camp J and Morty RE: Recent advances in late lung development and the pathogenesis of bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol. 305:L893–L905. 2013. View Article : Google Scholar : PubMed/NCBI
9	Du T and Zamore PD: microPrimer: the biogenesis and function of microRNA. Development. 132:4645–4652. 2005. View Article : Google Scholar : PubMed/NCBI
10	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
11	Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
12	Dong J, Jiang G, Asmann YW, Tomaszek S, Jen J, Kislinger T and Wigle DA: MicroRNA networks in mouse lung organogenesis. PLoS One. 5:e108542010. View Article : Google Scholar : PubMed/NCBI
13	Tay HL, Plank M, Collison A, Mattes J, Kumar RK and Foster PS: MicroRNA: potential biomarkers and therapeutic targets for allergic asthma? Ann Med. 46:633–639. 2014. View Article : Google Scholar : PubMed/NCBI
14	Lino Cardenas CL, Kaminski N and Kass DJ: Micromanaging microRNAs: using murine models to study microRNAs in lung fibrosis. Drug Discov Today Dis Models. 10:e145–e151. 2013. View Article : Google Scholar
15	Joshi P, Middleton J, Jeon YJ and Garofalo M: MicroRNAs in lung cancer. World J Methodol. 4:59–72. 2014. View Article : Google Scholar : PubMed/NCBI
16	Lu Y, Thomson JM, Wong HY, Hammond SM and Hogan BL: Transgenic overexpression of the microRNA miR-17-92 cluster promotes proliferation and inhibits differentiation of lung epithelial progenitor cells. Dev Biol. 310:442–453. 2007. View Article : Google Scholar : PubMed/NCBI
17	Ventura A, Young AG, Winslow MM, Lintault L, Meissner A, Erkeland SJ, Newman J, Bronson RT, Crowley D, Stone JR, et al: Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell. 132:875–886. 2008. View Article : Google Scholar : PubMed/NCBI
18	Carraro G, El-Hashash A, Guidolin D, Tiozzo C, Turcatel G, Young BM, De Langhe SP, Bellusci S, Shi W, Parnigotto PP and Warburton D: miR-17 family of microRNAs controls FGF10-mediated embryonic lung epithelial branching morphogenesis through MAPK14 and STAT3 regulation of E-Cadherin distribution. Dev Biol. 333:238–250. 2009. View Article : Google Scholar : PubMed/NCBI
19	Navarro A, Marrades RM, Viñolas N, Quera A, Agustí C, Huerta A, Ramirez J, Torres A and Monzo M: MicroRNAs expressed during lung cancer development are expressed in human pseudoglandular lung embryogenesis. Oncology. 76:162–169. 2009. View Article : Google Scholar : PubMed/NCBI
20	Bhaskaran M, Wang Y, Zhang H, Weng T, Baviskar P, Guo Y, Gou D and Liu L: MicroRNA-127 modulates fetal lung development. Physiol Genomics. 37:268–278. 2009. View Article : Google Scholar : PubMed/NCBI
21	Zhang X, Peng W, Zhang S, Wang C, He X, Zhang Z, Zhu L, Wang Y and Feng Z: MicroRNA expression profile in hyperoxia-exposed newborn mice during the development of bronchopulmonary dysplasia. Respir Care. 56:1009–1015. 2011. View Article : Google Scholar : PubMed/NCBI
22	Yang H, Fu J, Xue X, Yao L, Qiao L, Hou A, Jin L and Xing Y: Epithelial-mesenchymal transitions in bronchopulmonary dysplasia of newborn rats. Pediatr Pulmonol. 49:1112–1123. 2014. View Article : Google Scholar : PubMed/NCBI
23	Northway WH Jr, Rosan RC and Porter DY: Pulmonary disease following respirator therapy of hyaline-membrane disease. Bronchopulmonary dysplasia. N Engl J Med. 276:357–368. 1967. View Article : Google Scholar : PubMed/NCBI
24	Bhaskaran M, Xi D, Wang Y, Huang C, Narasaraju T, Shu W, Zhao C, Xiao X, More S, Breshears M and Liu L: Identification of microRNAs changed in the neonatal lungs in response to hyperoxia exposure. Physiol Genomics. 44:970–980. 2012. View Article : Google Scholar : PubMed/NCBI
25	Dong J, Carey WA, Abel S, Collura C, Jiang G, Tomaszek S, Sutor S, Roden AC, Asmann YW, Prakash YS and Wigle DA: MicroRNA-mRNA interactions in a murine model of hyperoxia-induced bronchopulmonary dysplasia. BMC Genomics. 13:2042012. View Article : Google Scholar : PubMed/NCBI
26	Narasaraju T, Shukla D, More S, Huang C, Zhang L, Xiao X and Liu L: Role of microRNA-150 and glycoprotein nonmetastatic melanoma protein B in angiogenesis during hyperoxia-induced neonatal lung injury. Am J Respir Cell Mol Biol. 52:253–261. 2015. View Article : Google Scholar
27	Gu H, Yang T, Fu S, Chen X, Guo L and Ni Y: MicroRNA-490-3p inhibits proliferation of A549 lung cancer cells by targeting CCND1. Biochem Biophys Res Commun. 444:104–108. 2014. View Article : Google Scholar : PubMed/NCBI
28	Bray I, Tivnan A, Bryan K, Foley NH, Watters KM, Tracey L, Davidoff AM and Stallings RL: MicroRNA-542-5p as a novel tumor suppressor in neuroblastoma. Cancer Lett. 303:56–64. 2011. View Article : Google Scholar : PubMed/NCBI
29	Song M, Yin Y, Zhang J, Zhang B, Bian Z, Quan C, Zhou L, Hu Y, Wang Q, Ni S, et al: MiR-139-5p inhibits migration and invasion of colorectal cancer by downregulating AMFR and NOTCH1. Protein Cell. 5:851–861. 2014. View Article : Google Scholar : PubMed/NCBI
30	Shen K, Mao R, Ma L, Li Y, Qiu Y, Cui D, Le V, Yin P, Ni L and Liu J: Post-transcriptional regulation of the tumor suppressor miR-139-5p and a network of miR-139-5p-mediated mRNA interactions in colorectal cancer. FEBS J. 281:3609–3624. 2014. View Article : Google Scholar : PubMed/NCBI
31	Liu R, Yang M, Meng Y, Liao J, Sheng J, Pu Y, Yin L and Kim SJ: Tumor-suppressive function of miR-139-5p in esophageal squamous cell carcinoma. PLoS One. 8:e770682013. View Article : Google Scholar : PubMed/NCBI
32	Krishnan K, Steptoe AL, Martin HC, Pattabiraman DR, Nones K, Waddell N, Mariasegaram M, Simpson PT, Lakhani SR, Vlassov A, et al: miR-139-5p is a regulator of metastatic pathways in breast cancer. RNA. 19:1767–1780. 2013. View Article : Google Scholar : PubMed/NCBI
33	Wang H, Li M, Zhang R, Wang Y, Zang W, Ma Y, Zhao G and Zhang G: Effect of miR-335 upregulation on the apoptosis and invasion of lung cancer cell A549 and H1299. Tumour Biol. 34:3101–3109. 2013. View Article : Google Scholar : PubMed/NCBI
34	Jiang H, Hua D, Zhang J, Lan Q, Huang Q, Yoon JG, Han X, Li L, Foltz G, Zheng S and Lin B: MicroRNA-127-3p promotes glioblastoma cell migration and invasion by targeting the tumor-suppressor gene SEPT7. Oncol Rep. 31:2261–2269. 2014.PubMed/NCBI
35	Jiang H, Jin C, Liu J, Hua D, Zhou F, Lou X, Zhao N, Lan Q, Huang Q, Yoon JG, et al: Next generation sequencing analysis of miRNAs: MiR-127-3p inhibits glioblastoma proliferation and activates TGF-beta signaling by targeting SKI. OMICS. 18:196–206. 2014. View Article : Google Scholar : PubMed/NCBI
36	Zha R, Guo W, Zhang Z, Qiu Z, Wang Q, Ding J, Huang S, Chen T, Gu J, Yao M and He X: Genome-wide screening identified that miR-134 acts as a metastasis suppressor by targeting integrin β1 in hepatocellular carcinoma. PLoS One. 9:e876652014. View Article : Google Scholar
37	Li H, Dai S, Zhen T, Shi H, Zhang F, Yang Y, Kang L, Liang Y and Han A: Clinical and biological significance of miR-378a-3p and miR-378a-5p in colorectal cancer. Eur J Cancer. 50:1207–1221. 2014. View Article : Google Scholar : PubMed/NCBI
38	Megiorni F, Cialfi S, McDowell HP, Felsani A, Camero S, Guffanti A, Pizer B, Clerico A, De Grazia A, Pizzuti A, et al: Deep Sequencing the microRNA profile in rhabdomyosarcoma reveals downregulation of miR-378 family members. BMC Cancer. 14:8802014. View Article : Google Scholar
39	Wu Z, Wu Y, Tian Y, Sun X, Liu J, Ren H, Liang C, Song L, Hu H, Wang L and Jiao B: Differential effects of miR-34c-3p and miR-34c-5p on the proliferation, apoptosis and invasion of glioma cells. Oncol Lett. 6:1447–1452. 2013.PubMed/NCBI
40	López JA and Alvarez-Salas LM: Differential effects of miR-34c-3p and miR-34c-5p on SiHa cells proliferation apoptosis, migration and invasion. Biochem Biophys Res Commun. 409:513–519. 2011. View Article : Google Scholar : PubMed/NCBI
41	Xu H, Liu C, Zhang Y, Guo X, Liu Z, Luo Z, Chang Y, Liu S, Sun Z and Wang X: Let-7b-5p regulates proliferation and apoptosis in multiple myeloma by targeting IGF1R. Acta Biochim Biophys Sin (Shanghai). 46:965–972. 2014. View Article : Google Scholar
42	Zhu YJ, Xu B and Xia W: Hsa-miR-182 downregulates RASA1 and suppresses lung squamous cell carcinoma cell proliferation. Clin Lab. 60:155–159. 2014.PubMed/NCBI
43	Stenvold H, Donnem T, Andersen S, Al-Saad S, Busund LT and Bremnes RM: Stage and tissue-specific prognostic impact of miR-182 in NSCLC. BMC Cancer. 14:1382014. View Article : Google Scholar : PubMed/NCBI
44	Yang WB, Chen PH, Hsu T, Fu TF, Su WC, Liaw H, Chang WC and Hung JJ: Sp1-mediated microRNA-182 expression regulates lung cancer progression. Oncotarget. 5:740–753. 2014. View Article : Google Scholar : PubMed/NCBI
45	Wang M1, Wang Y, Zang W, Wang H, Chu H, Li P, Li M, Zhang G and Zhao G: Downregulation of microRNA-182 inhibits cell growth and invasion by targeting programmed cell death 4 in human lung adenocarcinoma cells. Tumour Biol. 35:39–46. 2014. View Article : Google Scholar
46	Zhang L, Liu T, Huang Y and Liu J: microRNA-182 inhibits the proliferation and invasion of human lung adenocarcinoma cells through its effect on human cortical actin-associated protein. Int J Mol Med. 28:381–388. 2011.PubMed/NCBI
47	Sun Y, Fang R, Li C, Li L, Li F, Ye X and Chen H: Hsa-miR-182 suppresses lung tumorigenesis through downregulation of RGS17 expression in vitro. Biochem Biophys Res Commun. 396:501–507. 2010. View Article : Google Scholar : PubMed/NCBI
48	Lei Z, Xu G, Wang L, Yang H, Liu X, Zhao J and Zhang HT: MiR-142-3p represses TGF-beta-induced growth inhibition through repression of TGFbetaR1 in non-small cell lung cancer. FASEB J. 28:2696–2704. 2014. View Article : Google Scholar : PubMed/NCBI
49	Carraro G, Shrestha A, Rostkovius J, Contreras A, Chao CM, El Agha E, Mackenzie B, Dilai S, Guidolin D, Taketo MM, et al: miR-142-3p balances proliferation and differentiation of mesenchymal cells during lung development. Development. 141:1272–1281. 2014. View Article : Google Scholar : PubMed/NCBI
50	Ress AL, Stiegelbauer V, Winter E, Schwarzenbacher D, Kiesslich T, Lax S, Jahn S, Deutsch A, Bauernhofer T, Ling H, et al: MiR-96-5p influences cellular growth and is associated with poor survival in colorectal cancer patients. Mol Carcinog. Sep 25–2014.Epub ahead of print. View Article : Google Scholar : PubMed/NCBI
51	Li C, Du X, Tai S, Zhong X, Wang Z, Hu Z, Zhang L, Kang P, Ji D, Jiang X, et al: GPC1 regulated by miR-96-5p, rather than miR-182-5p, in inhibition of pancreatic carcinoma cell proliferation. Int J Mol Sci. 15:6314–6327. 2014. View Article : Google Scholar : PubMed/NCBI