Volume 10, Issue 3 (2019)                   JMBS 2019, 10(3): 425-432 | Back to browse issues page

XML Persian Abstract Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Shariari F, Moradi S, Totonchi M, Satarian L, mowla S, Baharvand H. Constructing microRNA-mRNA Integrative Network of miR-204-5p and miR-211-5p in RPE Cells Going Through EMT. JMBS 2019; 10 (3) :425-432
URL: http://biot.modares.ac.ir/article-22-23558-en.html
1- Molecular Genetics Department, Biological Sciences Faculty, Trabiat Modares Tehran, Iran
2- Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research (ACECR), Tehran, Iran
3- Molecular Genetics Department, Biological Sciences Faculty, Trabiat Modares Tehran, Iran, Tarbiat Modares University, Nasr Bridge, Jalal-Al-Ahmad Highway, Tehran, Iran.
Abstract:   (4291 Views)
Aims: The retinal pigment epithelium cells (RPE) have crucial roles in the health and functionality of retina. Any damage or dysfunction of these cells can lead to severe retinopathies. Identification of signaling pathways and biological processes involved in RPE differentiation can be useful in devising more robust therapeutic approaches.
Materials and Methods: In the present study, we used the intersection of three online prediction databases and their ::union:: with one experimental database to select microRNAs gene targets. Next, by the intersect of the targeted genes with an increase in their expression in epithelial to mesenchymal transition (EMT) of RPE cells, we tried to build a microRNA-mRNA integrative network. Further, several pathway analyses tools were used to perform a more accurate and comprehensive analysis of the signaling pathways and biological processes being regulated by selected miRs in the EMT of the RPE cells.
Findings: Our study revealed that among the 3406 genes being upregulated over the course of EMT in RPE cells, adj p-value≤0.05, fold change≥1.5, 93 genes were miR-204-5p and miR 211-5p target genes. Further analysis of the obtained target gene list demonstrated that these two microRNAs are mostly involved in maintaining RPE cells from going through EMT via regulation of cell adhesion and secretion subnetworks and also MAPK and TGF-β1 signaling pathways while preserving cells from apoptosis and neuronal fates.
Conclusion: This study indicated that miR-204-5p and miR 211-5p are involved in protecting RPE cells from EMT and reinforce their epithelial cell identity.
Full-Text [PDF 1028 kb]   (2650 Downloads)    
Article Type: Original Research | Subject: Molecular biotechnology
Received: 2018/07/27 | Accepted: 2018/12/1 | Published: 2019/09/21

1. Klein R, Chou CF, Klein BE, Zhang X, Meuer SM, Saaddine JB. Prevalence of age-related macular degeneration in the US population. Arch Ophthalmol. 2011;129(1):75-80. [Link] [DOI:10.1001/archophthalmol.2010.318]
2. Colijn JM, Buitendijk GHS, Prokofyeva E, Alves D, Cachulo ML, Khawaja AP, et al. Prevalence of age-related macular degeneration in europe: the past and the future. Ophthalmology. 2017;124(12):1753-63. [Link] [DOI:10.1016/j.ophtha.2017.05.035]
3. Guo H, Ingolia NT, Weissman JS, Bartel DP. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 2010;466(7308):835-40. [Link] [DOI:10.1038/nature09267]
4. Lee EJ, Baek M, Gusev Y, Brackett DJ, Nuovo GJ, Schmittgen TD. Systematic evaluation of microRNA processing patterns in tissues, cell lines, and tumors. RNA. 2008;14(1):35-42. [Link] [DOI:10.1261/rna.804508]
5. Selbach M, Schwanhäusser B, Thierfelder N, Fang Z, Raya Khanin R, Rajewsky N. Widespread changes in protein synthesis induced by microRNAs. Nature. 2008;455(7209):58-63. [Link] [DOI:10.1038/nature07228]
6. Linsley PS, Schelter J, Burchard J, Kibukawa M, Martin MM, Bartz SR, et al. Transcripts targeted by the microRNA-16 family cooperatively regulate cell cycle progression. Mol Cell Biol. 2007;27(6):2240-52. [Link] [DOI:10.1128/MCB.02005-06]
7. Brennecke J, Stark A, Russell RB, Cohen SM. Principles of microRNA-target recognition. PLoS Biol. 2005;3(3):e85. [Link] [DOI:10.1371/journal.pbio.0030085]
8. Shkumatava A, Stark A, Sive H, Bartel DP. Coherent but overlapping expression of microRNAs and their targets during vertebrate development. Genes Dev. 2009;23(4):466-81. [Link] [DOI:10.1101/gad.1745709]
9. Mishima T, Akagi I, Miyashita M, Ishibashi O, Mizuguchi Y, Tajiri T, et al. Study of MicroRNA expression profiles of esophageal cancer. J Nippon Med Sch. 2009;76(1):43. [Link] [DOI:10.1272/jnms.76.43]
10. Kitano H. Biological robustness. Nat Rev Genet. 2004;5(11):826-37. [Link] [DOI:10.1038/nrg1471]
11. Mukherji S, Ebert MS, Zheng GX, Tsang JS, Sharp PA, van Oudenaarden A. MicroRNAs can generate thresholds in target gene expression. Nat Genet. 2011;43(9):854-9. [Link] [DOI:10.1038/ng.905]
12. Gullapalli VK, Sugino IK, Van Patten Y, Shah S, Zarbin MA. Impaired RPE survival on aged submacular human Bruch's membrane. Exp Eye Res. 2005;80(2):235-48. [Link] [DOI:10.1016/j.exer.2004.09.006]
13. Radeke MJ, Radeke CM, Shih YH, Hu J, Bok D, Johnson LV, et al. Restoration of mesenchymal retinal pigmented epithelial cells by TGFbeta pathway inhibitors: implications for age-related macular degeneration. Genome Med. 2015;7(1):58. [Link] [DOI:10.1186/s13073-015-0183-x]
14. Adijanto J, Castorino JJ, Grunwald GB, Philp NJ. MicroRNAs 204/211 promotes differentiation of human retinal pigment epithelial (RPE) cells. Investig Ophthalmol Visual Sci. 2012;53(14):1129. [Link] [DOI:10.4016/40383.01]
15. Adijanto J, Castorino JJ, Wang ZX, Maminishkis A, Grunwald GB, Philp NJ. Microphthalmia-associated transcription factor (MITF) promotes differentiation of human retinal pigment epithelium (RPE) by regulating microRNAs-204/211 expression. J Biol Chem. 2012;287(24):20491-503. [Link] [DOI:10.1074/jbc.M112.354761]
16. Rouillard AD, Gundersen GW, Fernandez NF, Wang Z, Monteiro CD, McDermott MG, et al. The harmonizome: a collection of processed datasets gathered to serve and mine knowledge about genes and proteins. Database. 2016;2016. [Link] [DOI:10.1093/database/baw100]
17. Tanihara H, Inatani M, Honda Y. Growth factors and their receptors in the retina and pigment epithelium. Prog Retin Eye Res. 1997;16(2):271-301. [Link] [DOI:10.1016/S1350-9462(96)00028-6]
18. Martin DM, Yee D, Feldman EL. Gene expression of the insulin-like growth factors and their receptors in cultured human retinal pigment epithelial cells. Brain Res Mol Brain Res. 1992;12(1-3):181-6. [Link] [DOI:10.1016/0169-328X(92)90082-M]
19. Campochiaro PA, Hackett SF, Vinores SA, Freund J, Csaky C, LaRochelle W, et al. Platelet-derived growth factor is an autocrine growth stimulator in retinal pigmented epithelial cells. J Cell Sci. 1994;107(Pt 9):2459-69. [Link]
20. Steele FR, Chader GJ, Johnson LV, Tombran-Tink J. Pigment epithelium-derived factor: neurotrophic activity and identification as a member of the serine protease inhibitor gene family. Proc Natl Acad Sci USA. 1993;90(4):1526-30. [Link] [DOI:10.1073/pnas.90.4.1526]
21. Witmer AN, Vrensen GF, Van Noorden CJ, Schlingemann RO. Vascular endothelial growth factors and angiogenesis in eye disease. Prog Retin Eye Res. 2003;22(1):1-29. [Link] [DOI:10.1016/S1350-9462(02)00043-5]
22. Ming M, Li X, Fan X, Yang D, Li L, Chen S, et al. Retinal pigment epithelial cells secrete neurotrophic factors and synthesize dopamine: possible contribution to therapeutic effects of RPE cell transplantation in Parkinson's disease. J Transl Med. 2009;7:53. [Link] [DOI:10.1186/1479-5876-7-53]
23. Ogata N, Wang L, Jo N, Tombran-Tink J, Takahashi K, Mrazek D, et al. Pigment epithelium derived factor as a neuroprotective agent against ischemic retinal injury. Curr Eye Res. 2001;22(4):245-52. [Link] [DOI:10.1076/ceyr.]
24. Ohana R, Weiman-Kelman B, Raviv S, Tamm ER, Pasmanik-Chor M, Rinon A, et al. MicroRNAs are essential for differentiation of the retinal pigmented epithelium and maturation of adjacent photoreceptors. Development. 2015;142(14):2487-98. [Link] [DOI:10.1242/dev.121533]
25. Newman AM, Gallo NB, Hancox LS, Miller NJ, Radeke CM, Maloney MA, et al. Systems-level analysis of age-related macular degeneration reveals global biomarkers and phenotype-specific functional networks. Genome Med. 2012;4(2):16. [Link] [DOI:10.1186/gm315]
26. Park CM, Hollenberg MJ. Basic fibroblast growth factor induces retinal regeneration in vivo. Dev Biol. 1989;134(1):201-5. [Link] [DOI:10.1016/0012-1606(89)90089-4]
27. Coulombre JL, Coulombre AJ. Regeneration of neural retina from the pigmented epithelium in the chick embryo. Dev Biol. 1965;12(1):79-92. [Link] [DOI:10.1016/0012-1606(65)90022-9]

Add your comments about this article : Your username or Email:

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.