Identification of pterygium-related long non-coding RNAs and expression profiling by microarray analysis

Liu,Jin; Ding,Xiangya; Yuan,Li; Zhang,Xiaojun

doi:10.3892/ijmm.2016.2641

Identification of pterygium-related long non-coding RNAs and expression profiling by microarray analysis

Authors:
- Jin Liu
- Xiangya Ding
- Li Yuan
- Xiaojun Zhang
View Affiliations

Affiliations: Department of Ophthalmology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210003, P.R. China, Department of Microbiology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
Published online on: June 14, 2016 https://doi.org/10.3892/ijmm.2016.2641
Pages: 529-536

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

Pterygium is a common degenerative and proliferative disease of the ocular surface. It becomes a significant sight-threatening complication once its ingrowth covers the pupil. The proliferative capacities of pterygial cells give pterygia the appearance of having a mechanism similar to tumorigenesis. Long non-coding RNAs (lncRNAs) are key regulators of gene expression. The expression levels of certain lncRNAs are associated with a number of diseases, such as different tumors and metabolic disorders, among others. However, the contributions of lncRNAs to pterygium remain largely unexplored. In this study, we constructed pterygium-related lncRNA libraries using microarray analysis to investigate the potential roles of lncRNAs in the development of pterygium. A total of 3,066 upregulated and 1,646 downregulated lncRNAs were identified in pterygium tissues compared with paired adjacent normal conjunctival tissues (log fold change >2.0). Quantitative polymerase chain reaction (qPCR) was performed to validate 3 upregulated and 2 downregulated lncRNAs in 10 patients. Bioinformatics analyses (Gene Ontology analysis and pathway analysis) were used for further research. Pathway analysis indicated that 82 pathways corresponded to the downregulated transcripts and that 15 pathways corresponded to the upregulated transcripts (p-value cut-off, 0.05). Our results reveal differentially expressed lncRNAs in pterygium and suggest that lncRNAs may be the novel molecular targets for the treatment of pterygium.

View Figures

View References

1	Engelsvold DH, Utheim TP, Olstad OK, Gonzalez P, Eidet JR, Lyberg T, Trøseid AM, Dartt DA and Raeder S: miRNA and mRNA expression profiling identifies members of the miR-200 family as potential regulators of epithelial-mesenchymal transition in pterygium. Exp Eye Res. 115:189–198. 2013. View Article : Google Scholar : PubMed/NCBI
2	Al-Swailem S, Xu Z, Wu L, Hartsock MJ, Yiu SC and Duh EJ: Induction of endothelial RAGE expression in pterygium. Mol Vis. 20:1740–1748. 2014.
3	Chui J, Coroneo MT, Tat LT, Crouch R, Wakefield D and Di Girolamo N: Ophthalmic pterygium: A stem cell disorder with premalignant features. Am J Pathol. 178:817–827. 2011. View Article : Google Scholar : PubMed/NCBI
4	Hirst LW, Axelsen RA and Schwab I: Pterygium and associated ocular surface squamous neoplasia. Arch Ophthalmol. 127:31–32. 2009. View Article : Google Scholar : PubMed/NCBI
5	Ando R, Kase S, Ohashi T, Dong Z, Fukuhara J, Kanda A, Murata M, Noda K, Kitaichi N and Ishida S: Tissue factor expression in human pterygium. Mol Vis. 17:63–69. 2011.PubMed/NCBI
6	Kato N, Shimmura S, Kawakita T, Miyashita H, Ogawa Y, Yoshida S, Higa K, Okano H and Tsubota K: Beta-catenin activation and epithelial-mesenchymal transition in the pathogenesis of pterygium. Invest Ophthalmol Vis Sci. 48:1511–1517. 2007. View Article : Google Scholar : PubMed/NCBI
7	Bradley JC, Yang W, Bradley RH, Reid TW and Schwab IR: The science of pterygia. Br J Ophthalmol. 94:815–820. 2010. View Article : Google Scholar
8	Chui J, Di Girolamo N, Wakefield D and Coroneo MT: The pathogenesis of pterygium: Current concepts and their therapeutic implications. Ocul Surf. 6:24–43. 2008. View Article : Google Scholar : PubMed/NCBI
9	Rinn JL and Chang HY: Genome regulation by long noncoding RNAs. Annu Rev Biochem. 81:145–166. 2012. View Article : Google Scholar : PubMed/NCBI
10	Ponting CP, Oliver PL and Reik W: Evolution and functions of long noncoding RNAs. Cell. 136:629–641. 2009. View Article : Google Scholar : PubMed/NCBI
11	Yan B, Wang ZH, Liu JY, Tao ZF, Li XM and Qin J: Long noncoding RNAs: Versatile players in biologcial processes and human disorders. Epigenomics. 6:375–379. 2014. View Article : Google Scholar : PubMed/NCBI
12	Hung T and Chang HY: Long noncoding RNA in genome regulation: Prospects and mechanisms. RNA Biol. 7:582–585. 2010. View Article : Google Scholar : PubMed/NCBI
13	Wang KC and Chang HY: Molecular mechanisms of long noncoding RNAs. Mol Cell. 43:904–914. 2011. View Article : Google Scholar : PubMed/NCBI
14	Huntley RP, Harris MA, Alam-Faruque Y, Blake JA, Carbon S, Dietze H, Dimmer EC, Foulger RE, Hill DP, Khodiyar VK, et al: A method for increasing expressivity of Gene Ontology annotations using a compositional approach. BMC Bioinformatics. 15:1552014. View Article : Google Scholar : PubMed/NCBI
15	Khatri P, Sirota M and Butte AJ: Ten years of pathway analysis: Current approaches and outstanding challenges. PLoS Comput Biol. 8:e10023752012. View Article : Google Scholar : PubMed/NCBI
16	Wu CW, Cheng YW, Hsu NY, Yeh KT, Tsai YY, Chiang CC, Wang WR and Tung JN: MiRNA-221 negatively regulated downstream p27Kip1 gene expression involvement in pterygium pathogenesis. Mol Vis. 20:1048–1056. 2014.PubMed/NCBI
17	Tung JN, Chiang CC, Tsai YY, Chou YY, Yeh KT, Lee H and Cheng YW: CyclinD1 protein expressed in pterygia is associated with β-catenin protein localization. Mol Vis. 16:2733–2738. 2010.PubMed/NCBI
18	Wang J, Liu X, Wu H, Ni P, Gu Z, Qiao Y, Chen N, Sun F and Fan Q: CREB upregulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer. Nucleic Acids Res. 38:5366–5383. 2010. View Article : Google Scholar : PubMed/NCBI
19	Huang JL, Ren TY, Cao SW, Zheng SH, Hu XM, Hu YW, Lin L, Chen J, Zheng L and Wang Q: HBx-related long non-coding RNA DBH-AS1 promotes cell proliferation and survival by activating MAPK signaling in hepatocellular carcinoma. Oncotarget. 6:33791–33804. 2015.PubMed/NCBI
20	Lazar V, Suo C, Orear C, van den Oord J, Balogh Z, Guegan J, Job B, Meurice G, Ripoche H, Calza S, et al: Integrated molecular portrait of non-small cell lung cancers. BMC Med Genomics. 6:532013. View Article : Google Scholar : PubMed/NCBI
21	Detorakis ET and Spandidos DA: Pathogenetic mechanisms and treatment options for ophthalmic pterygium: Trends and perspectives (Review). Int J Mol Med. 23:439–447. 2009. View Article : Google Scholar : PubMed/NCBI
22	Mauro J and Foster CS: Pterygia: Pathogenesis and the role of subconjunctival bevacizumab in treatment. Semin Ophthalmol. 24:130–134. 2009. View Article : Google Scholar : PubMed/NCBI
23	Hong S, Choi JY, Lee HK, Seong GJ, Seo KY, Kim EK and Byeon SH: Expression of neurotrophic factors in human primary pterygeal tissue and selective TNF-alpha-induced stimulation of ciliary neurotrophic factor in pterygeal fibroblasts. Exp Toxicol Pathol. 60:513–520. 2008. View Article : Google Scholar : PubMed/NCBI
24	O'Donoghue LE, Ptitsyn AA, Kamstock DA, Siebert J, Thomas RS and Duval DL: Expression profiling in canine osteosarcoma: Identification of biomarkers and pathways associated with outcome. BMC Cancer. 10:5062010. View Article : Google Scholar : PubMed/NCBI