Differentially expressed miRNAs in oxygen‑induced retinopathy newborn mouse models

Wang,Yunpeng; Wu,Suying; Yang,Yang; Peng,Fen; Li,Qintao; Tian,Peng; Xiang,Erying; Liang,Honglu; Wang,Beibei; Zhou,Xiaoyu; Huang,Hua; Zhou,Xiaoguang

doi:10.3892/mmr.2016.5993

Differentially expressed miRNAs in oxygen‑induced retinopathy newborn mouse models

Authors:
- Yunpeng Wang
- Suying Wu
- Yang Yang
- Fen Peng
- Qintao Li
- Peng Tian
- Erying Xiang
- Honglu Liang
- Beibei Wang
- Xiaoyu Zhou
- Hua Huang
- Xiaoguang Zhou
View Affiliations

Affiliations: Department of Neonatology, Nanshan People's Hospital, Affiliated to Guangdong Medical University, Shenzhen, Guangdong 518052, P.R. China, Department of Neonatology, University Hospital of Hubei Minzu University, Enshi, Hubei 445000, P.R. China, Department of Neonatology, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China
Published online on: December 6, 2016 https://doi.org/10.3892/mmr.2016.5993
Pages: 146-152
Copyright: © Wang 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

The present study aimed to identify microRNAs (miRNAs) involved in regulating retinal neovascularization and retinopathy of prematurity (ROP). A total of 80 healthy C57BL/6 neonatal mice were randomly divided into the oxygen‑induced retinopathy (OIR) group (n=40), in which 7‑day‑old mice were maintained in 75% oxygen conditions for 5 days, or the control group (n=40). Following collection of retinal tissue, retinal angiography and hematoxylin and eosin (H&E) staining were performed. Total RNA was also extracted from retinal tissue, and miRNA microarrays and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) were performed to identify differentially expressed miRNAs in the two groups. Retinal angiography and H&E staining revealed damage to retinas in the OIR group. Compared with the control group, 67 miRNAs were differentially expressed in the OIR group, of which 34 were upregulated and 33 were downregulated. Of these differentially expressed miRNAs, 32 exhibited a fold change ≥2, of which 21 were upregulated and 11 were downregulated. The results of RT‑qPCR for miR‑130a‑3p and miR‑5107‑5p were in accordance with those of the miRNA microarray. The newly identified miRNAs may be important in the development of ROP, and may provide a basis for future research into the mechanisms of ROP.

View Figures

View References

1	McGregor ML, Bremer DL, Cole C, McClead RE, Phelps DL, Fellows RR and Oden N: HOPE-ROP Multicenter Group. High Oxygen Percentage in Retinopathy of Prematurity study: Retinopathy of prematurity outcome in infants with prethreshold retinopathy of prematurity and oxygen saturation >94% in room air: The high oxygen percentage in retinopathy of prematurity study. Pediatrics. 110:540–544. 2002. View Article : Google Scholar : PubMed/NCBI
2	Sola A, Chow L and Rogido M: Retinopathy of prematurity and oxygen therapy: A changing relationship. An Pediatr (Barc). 62:48–63. 2005.(In spanish). PubMed/NCBI
3	Chamney S, McGrory L, McCall E, Twaij S, Napier M, Rollins R, Marshall AH, Craig S and McLoone E: Treatment of retinopathy of prematurity in Northern Ireland, 2000–2011: A population-based study. J AAPOS. 19:223–227. 2015. View Article : Google Scholar : PubMed/NCBI
4	Levesque BM, Kalish LA, Winston AB, Parad RB, Hernandez-Diaz S, Phillips M, Zolit A, Morey J, Gupta M, Mammoto A, et al: Low urine vascular endothelial growth factor levels are associated with mechanical ventilation, bronchopulmonary dysplasia and retinopathy of prematurity. Neonatology. 104:56–64. 2013. View Article : Google Scholar : PubMed/NCBI
5	Patel S Jivabhai, Bany-Mohammed F, McNally L, Valencia GB, Lazzaro DR, Aranda JV and Beharry KD: Exogenous superoxide dismutase mimetic without scavenging H₂O₂ causes photoreceptor damage in a rat model for oxygen-induced retinopathy. Invest Ophthalmol Vis Sci. 56:1665–1677. 2015. View Article : Google Scholar : PubMed/NCBI
6	Penn JS, Tolman BL and Henry MM: Oxygen-induced retinopathy in the rat: Relationship of retinal nonperfusion to subsequent neovascularization. Invest Ophthalmol Vis Sci. 35:3429–3435. 1994.PubMed/NCBI
7	Smith LE, Wesolowski E, McLellan A, Kostyk SK, D'Amato R, Sullivan R and D'Amore PA: Oxygen-induced retinopathy in the mouse. Invest Ophthalmol Vis Sci. 35:101–111. 1994.PubMed/NCBI
8	Sato T, Kusaka S, Hashida N, Saishin Y, Fujikado T and Tano Y: Comprehensive gene-expression profile in murine oxygen-induced retinopathy. Br J Ophthalmol. 93:96–103. 2009. View Article : Google Scholar : PubMed/NCBI
9	Bentwich I, Avniel A, Karov Y, Aharonov R, Gilad S, Barad O, Barzilai A, Einat P, Einav U, Meiri E, et al: Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet. 37:766–770. 2005. View Article : Google Scholar : PubMed/NCBI
10	Xie M, Zhang S and Yu B: microRNA biogenesis, degradation and activity in plants. Cell Mol Life Sci. 72:87–99. 2015. View Article : Google Scholar : PubMed/NCBI
11	Doench JG and Sharp PA: Specificity of microRNA target selection in translational repression. Genes Dev. 18:504–511. 2004. View Article : Google Scholar : PubMed/NCBI
12	Kuhnert F, Mancuso MR, Hampton J, Stankunas K, Asano T, Chen CZ and Kuo CJ: Attribution of vascular phenotypes of the murine Egfl7 locus to the microRNA miR-126. Development. 135:3989–3993. 2008. View Article : Google Scholar : PubMed/NCBI
13	Chen Y and Gorski DH: Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenichomeobox genes GAX and HOXA5. Blood. 111:1217–1226. 2008.PubMed/NCBI
14	Kuehbacher A, Urbich C, Zeiher AM and Dimmeler S: Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis. Circ Res. 101:59–68. 2007. View Article : Google Scholar : PubMed/NCBI
15	Johnson CD, Esquela-Kerscher A, Stefani G, Byrom M, Kelnar K, Ovcharenko D, Wilson M, Wang X, Shelton J, Shingara J, et al: The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Res. 67:7713–7722. 2007. View Article : Google Scholar : PubMed/NCBI
16	Shen J, Yang X, Xie B, Chen Y, Swaim M, Hackett SF and Campochiaro PA: MicroRNAs regulate ocular neovascularization. Mol Ther. 16:1208–1216. 2008. View Article : Google Scholar : PubMed/NCBI
17	Bai Y, Bai X, Wang Z, Zhang X, Ruan C and Miao J: MicroRNA-126 inhibits ischemia-induced retinal neovascularization via regulating angiogenic growth factors. Exp Mol Pathol. 91:471–477. 2011. View Article : Google Scholar : PubMed/NCBI
18	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C (T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
19	Wang W, Li Z, Sato T and Oshima Y: Tenomodulin inhibits retinal neovascularization in a mouse model of oxygen-induced retinopathy. Int J Mol Sci. 13:15373–15386. 2012. View Article : Google Scholar : PubMed/NCBI
20	Xia C, Cai Y, Lin Y, Guan R, Xiao G and Yang J: MiR-133b-5p regulates the expression of the heat shock protein 70 during rat neuronal cell apoptosis induced by the gp120 V3 loop peptide. J Med Virol. 88:437–447. 2015.PubMed/NCBI
21	Rérole AL, Jego G and Garrido C: Hsp70: Anti-apoptotic and tumorigenic protein. Methods. 787:205–230. 2011.
22	Zhao H, Li M, Li L, Yang X, Lan G and Zhang Y: MiR-133b is down-regulated in human osteosarcoma and inhibits osteosarcoma cells proliferation, migration, and invasion and promotes apoptosis. PLoS One. 8:e835712013. View Article : Google Scholar : PubMed/NCBI
23	Noh SJ, Miller SH, Lee YT, Goh SH, Marincola FM, Stroncek DF, Reed C, Wang E and Miller JL: Let-7 microRNAs are developmentally regulated in circulating human erythroid cells. J Transl Med. 7:982009. View Article : Google Scholar : PubMed/NCBI
24	Landskroner-Eiger S, Moneke I and Sessa WC: miRNAs as modulators of angiogenesis. Cold Spring Harb Perspect Med. 3:a0066432013.PubMed/NCBI
25	Vaz F, Hanenberg H, Schuster B, Barker K, Wiek C, Erven V, Neveling K, Endt D, Kesterton I, Autore F, et al: Mutation of the RAD51C gene in a Fanconi anemia-like disorder. Nat Genet. 42:406–409. 2010. View Article : Google Scholar : PubMed/NCBI
26	Wang S, Tang Y, Cui H, Zhao X, Luo X, Pan W, Huang X and Shen N: Let-7/miR-98 regulate Fas and Fas-mediated apoptosis. Genes Immun. 12:149–154. 2011. View Article : Google Scholar : PubMed/NCBI
27	Ulivi P, Foschi G, Mengozzi M, Scarpi E, Silvestrini R, Amadori D and Zoli W: Peripheral Blood mir-328 expression as a potential biomarker for the early diagnosis of NSCLC. Int J Mol Sci. 14:10332–10342. 2013. View Article : Google Scholar : PubMed/NCBI
28	Arora S, Ranade AR, Tran NL, Nasser S, Sridhar S, Korn RL, Ross JT, Dhruv H, Foss KM, Sibenaller Z, et al: MicroRNA-328 is associated with (non-small) cell lung cancer (NSCLC) brain metastasis and mediates NSCLC migration. Int J Cancer. 129:2621–2631. 2011. View Article : Google Scholar : PubMed/NCBI
29	Okumus NO, Gursel B, Meydan D, Ozdemir O, Odabas E and Gonullu G: Prognostic significance of concomitant radiotherapy in newly diagnosed glioblastomamultiforme: A multivariate analysis of 116 patients. Ann Saudi Med. 32:250–255. 2012.PubMed/NCBI
30	Delic S, Lottmann N, Stelzl A, Liesenberg F, Wolter M, Götze S, Zapatka M, Shiio Y, Sabel MC, Felsberg J, et al: MiR-328 promotes glioma cell invasion via SFRP1-dependent Wnt-signaling activation. Neuro Oncol. 16:179–190. 2014. View Article : Google Scholar : PubMed/NCBI
31	Kozomara A and Griffiths-Jones S: miRBase: Annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res. 42:D68–D73. 2014. View Article : Google Scholar : PubMed/NCBI
32	Brafman A, Mett I, Shafir M, Gottlieb H, Damari G, Gozlan-Kelner S, Vishnevskia-Dai V, Skaliter R, Einat P, Faerman A, et al: Inhibition of oxygen-induced retinopathy in RTP801-deficient mice. Invest Ophthalmol Vis Sci. 45:3796–3805. 2004. View Article : Google Scholar : PubMed/NCBI
33	Nidadavolu LS, Niedernhofer LJ and Khan SA: Identification of microRNAs dysregulated in cellular senescence driven by endogenous genotoxicstress. Aging (Albany NY). 5:460–473. 2013.PubMed/NCBI
34	Huang JY, Chou SF, Lee JW, Chen HL, Chen CM, Tao MH and Shih C: MicroRNA-130a can inhibit hepatitis B virus replication via targeting PGC1α and PPARγ. RNA. 21:385–400. 2015. View Article : Google Scholar : PubMed/NCBI
35	Tawfik A, Sanders T, Kahook K, Akeel S, Elmarakby A and Al-Shabrawey M: Suppression of retinal peroxisome proliferator-activated receptor gamma in experimental diabetes and oxygen-induced retinopathy: Role of NADPH oxidase. Invest Ophthalmol Vis Sci. 50:878–884. 2009. View Article : Google Scholar : PubMed/NCBI
36	Simpson-Haidaris PJ, Pollock SJ, Ramon S, Guo N, Woeller CF, Feldon SE and Phipps RP: Anticancer role of PPARgamma agonists in hematological malignancies found in the vasculature, marrow and eyes. PPAR Res. 2010:8146092010.PubMed/NCBI