Involvement of dysregulated coding and long non‑coding RNAs in the pathogenesis of strabismus

Ma,Wen‑Xiu; Huang,Xiao‑Gang; Yang,Tian‑Ke; Yao,Jing‑Yan

doi:10.3892/mmr.2018.8832

Involvement of dysregulated coding and long non‑coding RNAs in the pathogenesis of strabismus

Authors:
- Wen‑Xiu Ma
- Xiao‑Gang Huang
- Tian‑Ke Yang
- Jing‑Yan Yao
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Affiliations: Department of Ophthalmology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China
Published online on: March 29, 2018 https://doi.org/10.3892/mmr.2018.8832
Pages: 7737-7745
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Strabismus is a common ocular disorder in children and may result in exterior abnormalities and impaired visual functions. However, the detailed pathogenesis of strabismus unclear. The present study assessed the comprehensive analyses on the roles of RNAs in the development of strabismus. The public datasets of strabismus and the corresponding control tissues were downloaded from the Gene Expression Omnibus (GEO). Reannotations of the dysregulated coding and long non‑coding RNAs (lncRNAs) and functional enrichments of the differently expressed genes (DEGs) were conducted. A total of 790 DEGs were screened (648 upregulated and 142 downregulated) in the present study. Among the DEGs, a total of 32 differently expressed lncRNAs were detected (14 upregulated and 18 downregulated). When the Gene Ontology (GO) enrichment was considered, it was identified that a total of 143 GO terms (82 for biological process, 31 for cellular component and 30 for molecular function) were identified. Among all the 57 detected Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, the phagosome pathway, which was labeled as hsa004145, demonstrated the most bioinformatics importance. However, most lncRNAs, except LINC01279 and LOC643733, indicated <3 target mRNAs and were not suitable for advanced bioinformatics analyses. Bioinformatics analyses demonstrated that there was a GO term for each lncRNA (proteinaceous extracellular for LINC01279 and cell surface for LOC643733). In conclusion, a set of coding RNA as well as lncRNAs differentially expressed in strabismus EOM samples were indicated. Notably, the present findings important information for advanced pathogenesis research and biomarkers detection.

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1	Lambert SR: Population-based incidence of strabismus: Why is it important? JAMA Ophthalmol. 135:1053–1054. 2017. View Article : Google Scholar : PubMed/NCBI
2	Shapira Y, Machluf Y, Mimouni M, Chaiter Y and Mezer E: Amblyopia and strabismus: Trends in prevalence and risk factors among young adults in Israel. Br J Ophthalmol. 2017.doi: 10.1136/bjophthalmol-2017-310364. PubMed/NCBI
3	Nelson LB: Macular changes following strabismus surgery confirmed by the use of optical coherence tomography. J Pediatr Ophthalmol Strabismus. 53:102016. View Article : Google Scholar : PubMed/NCBI
4	Lindstrom M, Tjust AE and Domellof Pedrosa F: Pax7-positive cells/satellite cells in human extraocular muscles. Invest Ophthalmol Vis Sci. 56:6132–6143. 2015. View Article : Google Scholar : PubMed/NCBI
5	Gong HM, Wang J, Xu J, Zhou ZY, Li JW and Chen SF: Identification of rare paired box 3 variant in strabismus by whole exome sequencing. Int J Ophthalmol. 10:1223–1228. 2017.PubMed/NCBI
6	Altick AL, Feng CY, Schlauch K, Johnson LA and von Bartheld CS: Differences in gene expression between strabismic and normal human extraocular muscles. Invest Ophthalmol Vis Sci. 53:5168–5177. 2012. View Article : Google Scholar : PubMed/NCBI
7	Wang H, Huo X, Yang XR, He J, Cheng L, Wang N, Deng X, Jin H, Wang N, Wang C, et al: STAT3-mediated upregulation of lncRNA HOXD-AS1 as a ceRNA facilitates liver cancer metastasis by regulating SOX4. Mol Cancer. 16:1362017. View Article : Google Scholar : PubMed/NCBI
8	Akhade VS, Pal D and Kanduri C: Long noncoding RNA: Genome organization and mechanism of action. Adv Exp Med Biol. 1008:47–74. 2017. View Article : Google Scholar : PubMed/NCBI
9	Aubert G, Strauss KA, Lansdorp PM and Rider NL: Defects in lymphocyte telomere homeostasis contribute to cellular immune phenotype in patients with cartilage-hair hypoplasia. J Allergy Clin Immunol. 140:1120–1129.e1. 2017. View Article : Google Scholar : PubMed/NCBI
10	Li Y, Xu F, Xiao H and Han F: Long noncoding RNA BDNF-AS inversely regulated BDNF and modulated high-glucose induced apoptosis in human retinal pigment epithelial cells. J Cell Biochem. 119:817–823. 2018. View Article : Google Scholar : PubMed/NCBI
11	Zhu W, Meng YF, Xing Q, Tao JJ, Lu J and Wu Y: Identification of lncRNAs involved in biological regulation in early age-related macular degeneration. Int J Nanomedicine. 12:7589–7602. 2017. View Article : Google Scholar : PubMed/NCBI
12	Ye Z, Li Z and He S: Long noncoding RNA associated competing endogenous RNAs are induced by clusterin in retinal pigment epithelial cells. Mol Med Rep. 16:8399–8405. 2017. View Article : Google Scholar : PubMed/NCBI
13	Dennis G Jr, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC and Lempicki RA: DAVID: Database for annotation, visualization and integrated discovery. Genome Biol. 4:P32003. View Article : Google Scholar : PubMed/NCBI
14	Kanehisa M, Sato Y, Kawashima M, Furumichi M and Tanabe M: KEGG as a reference resource for gene and protein annotation. Nucleic Acids Res. 44:D457–D462. 2016. View Article : Google Scholar : PubMed/NCBI
15	von Mering C, Huynen M, Jaeggi D, Schmidt S, Bork P and Snel B: STRING: A database of predicted functional associations between proteins. Nucleic Acids Res. 31:258–261. 2003. View Article : Google Scholar : PubMed/NCBI
16	Franz M, Lopes CT, Huck G, Dong Y, Sumer O and Bader GD: Cytoscape.js: A graph theory library for visualisation and analysis. Bioinformatics. 32:309–311. 2016.PubMed/NCBI
17	Langfelder P and Horvath S: WGCNA: An R package for weighted correlation network analysis. BMC Bioinformatics. 9:5592008. View Article : Google Scholar : PubMed/NCBI
18	Ye XC, Pegado V, Patel MS and Wasserman WW: Strabismus genetics across a spectrum of eye misalignment disorders. Clin Genet. 86:103–111. 2014. View Article : Google Scholar : PubMed/NCBI
19	Lueder GT: Orbital causes of incomitant strabismus. Middle East Afr J Ophthalmol. 22:286–291. 2015. View Article : Google Scholar : PubMed/NCBI
20	Min X, Fan H, Zhao G and Liu G: Identification of 2 potentially relevant gene mutations involved in strabismus using whole-exome sequencing. Med Sci Monit. 23:1719–1724. 2017. View Article : Google Scholar : PubMed/NCBI
21	Rajab GZ, Suh SY and Demer JL: Magnetic resonance imaging in dissociated strabismus complex demonstrates generalized hypertrophy of rectus extraocular muscles. J AAPOS. 21:205–209. 2017. View Article : Google Scholar : PubMed/NCBI
22	Haider AS: Unilateral internuclear ophthalmoplegia, strabismus and transient torsional nystagmus in focal pontine infarction. BMJ Case Rep. 2016:bcr20162165032016. View Article : Google Scholar : PubMed/NCBI
23	Agarwal AB, Feng CY, Altick AL, Quilici DR, Wen D, Johnson LA and von Bartheld CS: Altered protein composition and gene expression in strabismic human extraocular muscles and tendons. Invest Ophthalmol Vis Sci. 57:5576–5585. 2016. View Article : Google Scholar : PubMed/NCBI
24	Schwalm S, Beyer S, Frey H, Haceni R, Grammatikos G, Thomas D, Geisslinger G, Schaefer L, Huwiler A and Pfeilschifter J: Sphingosine kinase-2 deficiency ameliorates kidney fibrosis by up-regulating Smad7 in a mouse model of unilateral ureteral obstruction. Am J Pathol. 187:2413–2429. 2017. View Article : Google Scholar : PubMed/NCBI
25	Saika S, Yamanaka O, Okada Y, Tanaka S, Miyamoto T, Sumioka T, Kitano A, Shirai K and Ikeda K: TGF beta in fibroproliferative diseases in the eye. Front Biosci (Schol Ed). 1:376–390. 2009. View Article : Google Scholar : PubMed/NCBI
26	Choi SU, Kim KW and Moon NJ: Effective treatment for prevention of post-operative adhesion after strabismus surgery in experimental rabbit model: 0.5% tranilast ophthalmic solution. BMC Ophthalmol. 16:1662016. View Article : Google Scholar : PubMed/NCBI
27	Mahan M and Engel JM: The resurgence of botulinum toxin injection for strabismus in children. Curr Opin Ophthalmol. 28:460–464. 2017. View Article : Google Scholar : PubMed/NCBI
28	McLoon LK, Christiansen SP, Ghose GM, Das VE and Mustari MJ: Improvement of eye alignment in adult strabismic monkeys by sustained IGF-1 treatment. Invest Ophthalmol Vis Sci. 57:6070–6078. 2016. View Article : Google Scholar : PubMed/NCBI
29	Levin R, Grinstein S and Canton J: The life cycle of phagosomes: Formation, maturation and resolution. Immunol Rev. 273:156–179. 2016. View Article : Google Scholar : PubMed/NCBI
30	Steinhauser C, Dallenga T, Tchikov V, Schaible UE, Schutze S and Reiling N: Immunomagnetic isolation of pathogen-containing phagosomes and apoptotic blebs from primary phagocytes. Curr Protoc Immunol. 105:14.36.1–26. 2014. View Article : Google Scholar
31	Russell DG: Phagosomes, fatty acids and tuberculosis. Nat Cell Biol. 5:776–778. 2003. View Article : Google Scholar : PubMed/NCBI
32	Jiang M, Esteve-Rudd J, Lopes VS, Diemer T, Lillo C, Rump A and Williams DS: Microtubule motors transport phagosomes in the RPE and lack of KLC1 leads to AMD-like pathogenesis. J Cell Biol. 210:595–611. 2015. View Article : Google Scholar : PubMed/NCBI
33	Chen YG, Satpathy AT and Chang HY: Gene regulation in the immune system by long noncoding RNAs. Nat Immunol. 18:962–972. 2017. View Article : Google Scholar : PubMed/NCBI
34	Zheng Y, Liu L and Shukla GC: A comprehensive review of web-based non-coding RNA resources for cancer research. Cancer Lett. 407:1–5. 2017. View Article : Google Scholar : PubMed/NCBI
35	Jarroux J, Morillon A and Pinskaya M: History, discovery and classification of lncRNAs. Adv Exp Med Biol. 1008:1–46. 2017. View Article : Google Scholar : PubMed/NCBI
36	Wan P, Su W and Zhuo Y: Precise long non-coding RNA modulation in visual maintenance and impairment. J Med Genet. 54:450–459. 2017. View Article : Google Scholar : PubMed/NCBI
37	Liu J, Ding X, Yuan L and Zhang X: Identification of pterygium-related long non-coding RNAs and expression profiling by microarray analysis. Int J Mol Med. 38:529–536. 2016. View Article : Google Scholar : PubMed/NCBI
38	Li F, Wen X, Zhang H and Fan X: Novel insights into the role of long noncoding RNA in ocular diseases. Int J Mol Sci. 17:4782016. View Article : Google Scholar : PubMed/NCBI
39	Gong C, Li Z, Ramanujan K, Clay I, Zhang Y, Lemire-Brachat S and Glass DJ: A long non-coding RNA, LncMyoD, regulates skeletal muscle differentiation by blocking IMP2-mediated mRNA translation. Dev Cell. 34:181–191. 2015. View Article : Google Scholar : PubMed/NCBI
40	Antunes-Foschini RS, Miyashita D, Bicas HE and McLoon LK: Activated satellite cells in medial rectus muscles of patients with strabismus. Invest Ophthalmol Vis Sci. 49:215–220. 2008. View Article : Google Scholar : PubMed/NCBI
41	Jin CF, Li Y, Ding XB, Li X, Zhang LL, Liu XF and Guo H: lnc133b, a novel, long non-coding RNA, regulates bovine skeletal muscle satellite cell proliferation and differentiation by mediating miR-133b. Gene. 630:35–43. 2017. View Article : Google Scholar : PubMed/NCBI
42	Tang R, Zhang G, Wang YC, Mei X and Chen SY: The long non-coding RNA GAS5 regulates transforming growth factor beta (TGF-beta)-induced smooth muscle cell differentiation via RNA Smad-binding elements. J Biol Chem. 292:14270–14278. 2017. View Article : Google Scholar : PubMed/NCBI