Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1
5-Year Impact Factor – 2.2
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Index Copernicus  – 161.11; MEiN – 140 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2018, vol. 27, nr 5, May, p. 577–582

doi: 10.17219/acem/69135

Publication type: original article

Language: English

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MiR-181a inhibits human trabecular meshwork cell apoptosis induced by H₂O₂ through the suppression of NF-κB and JNK pathways

Yuwen Wang1,A,D,F, Heding Zhou1,B,D,F, Xiaotian Liu1,C,D,F, Yin Han1,B,F, Suqi Pan1,B,F, Yanyan Wang1,C,F

1 Ningbo Eye Hospital, Ningbo, China


Background. The trabecular meshwork (TM) plays a critical role in the outflow of aqueous humor.
Objectives. In this study, we aimed to investigate the effect of miR-181a on H2O2-induced apoptosis in TM cells.
Material and Methods. Human primary explant-derived TM cells were cultured in fibroblast medium and then treated with different concentrations of H2O2 for 2 h. We used a series of methods to carry out the research, such as MTT assay, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), apoptosis assay, and western blot methodology.
Results. The apoptosis assay and qRT-PCR showed that H2O2-induced apoptosis and cell viability were suppressed in a dose-dependent manner in TM cells. After the TM cells were treated with H2O2, miR-181a expression was significantly lower. The overexpression of miR-181a enhanced TM cells’ viability, while the knockdown of miR-181a inhibited viability of cells. The overexpression of miR-181a suppressed TM cell apoptosis, while the knockdown of miR-181a induced apoptosis. H2O2 activated the nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) pathways and induced cell apoptosis, while the overexpression of miR-181a suppressed both pathways and decreased the rate of apoptosis.
Conclusion. In conclusion, this study indicated that miR-181a could improve the survival rate of TM cells after H2O2 treatment by blocking the NF-κB and JNK signaling pathways. These findings might provide novel therapeutic opportunities in the treatment of glaucoma.

Key words

cell apoptosis, H2O2, miR-181a, trabecular meshwork, nuclear factor-κB, c-Jun N-terminal kinase pathway

References (28)

  1. Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY. Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis: Ophthalmology. 2014:121:2081–2090.
  2. Cook C, Foster P. Epidemiology of glaucoma: What’s new? Can J Ophthalmol. 2012:47:223–226.
  3. Li A, Chi TL, Peterson-Yantorno K, Stamer WD, Mitchell CH, Civan MM. Mechanisms of ATP release by human trabecular meshwork cells, the enabling step in purinergic regulation of aqueous humor outflow. J Cell Physiol. 2012;227:172–182.
  4. Luna C, Li G, Huang J, et al. Regulation of trabecular meshwork cell contraction and intraocular pressure by miR-200c. Plos One. 2012;7:e51688.
  5. Awaikasaoka N, Inoue T, Kameda T, Fujimoto T, Inouemochita M, Tanihara H. Oxidative stress response signaling pathways in trabecular meshwork cells and their effects on cell viability. Mol Vis. 2013;19:1332–1340.
  6. Pillai RS. MicroRNA function: Multiple mechanisms for a tiny RNA? RNA. 2005;11:1753–1761.
  7. Ali NM, Boo L, Yeap SK, et al. Probable impact of age and hypoxia on proliferation and microRNA expression profile of bone marrow-derived human mesenchymal stem cells. PeerJ. 2016;4:e1536
  8. Di LG, Croce CM. miRNA profiling of cancer. Curr Opin Genet Dev. 2013;23:3–11.
  9. Nie Y, Han BM, Liu XB, et al. Identification of microRNAs involved in hypoxia- and serum deprivation-induced apoptosis in mesenchymal stem cells. Int J Biol Sci. 2010;7:762–768.
  10. Tomé M, López-Romero P, Albo C, et al. miR-335 orchestrates cell proliferation, migration and differentiation in human mesenchymal stem cells. Cell Death Differ. 2011;18:985–995.
  11. Kong N, Lu X, Li B. Downregulation of microRNA-100 protects apoptosis and promotes neuronal growth in retinal ganglion cells. BMC Mol Biol. 2014;15:25–25.
  12. Raghunath A, Perumal E. Micro-RNAs and their roles in eye disorders. Ophthal Res. 2015;53:169–186.
  13. Tanaka Y, Tsuda S, Kunikata H, et al. Profiles of extracellular miRNAs in the aqueous humor of glaucoma patients assessed with a microarray system. Sci Rep. 2014;4:633–633.
  14. Dismuke WM, Challa P, Navarro I, Stamer WD, Liu Y. Human aqueous humor exosomes. Exp Eye Res. 2015;132:73–77.
  15. He S, Zeng S, Zhou ZW, He ZX, Zhou SF. Hsa-microRNA-181a is a regulator of a number of cancer genes and a biomarker for endometrial carcinoma in patients: A bioinformatic and clinical study and the therapeutic implication. Drug Des Devel Ther. 2015;9:1103–1175.
  16. Dragu DL, Necula LG, Bieotu C, et al. Therapies targeting cancer stem cells: Current trends and future challenges. World J Stem Cells. 2015;7:1185–1201.
  17. Nakamura A, Rampersand YR, Sharma A, et al. Identification of microRNA-181a-5p and microRNA-4454 as mediators of facet cartilage degeneration. JCI Insight. 2016;1:e86820.
  18. Brodie C, Buchris E, Lee HK. miRNA Expression and Functions in Glioma and Glioma Stem Cells. MicroRNA Targeted Cancer Therapy. 2014;112:225–231.
  19. Thalyana Smith-Vikos FJS. MicroRNAs and their roles in aging. J Cell Sci. 2012;125:7–17.
  20. Parikh A, Lee C, Joseph P, et al. MicroRNA-181a has a critical role in ovarian cancer progression through the regulation of the epithelial-mesenchymal transition. Nat Commun. 2014;5:149–168.
  21. Takahashi E, Inoue T, Fujimoto T, Kojima S, Tanihara H. Epithelial mesenchymal transition-like phenomenon in trabecular meshwork cells. Exp Eye Res. 2014;118:72–79.
  22. Kozloski GA, Jiang X, Bhatt S, et al. MiR-181a negatively regulates NF-κB signaling and affects activated B-cell like diffuse large B-cell lymphoma pathogenesis. Blood. 2016;127(23):2856–2866.
  23. Guo LJ, Zhang QY. Decreased serum miR-181a is a potential new tool for breast cancer screening. Int J Mol Med. 2012;30:680–687.
  24. Bowie A, O’Neill LA. Oxidative stress and nuclear factor-κB activation A reassessment of the evidence in the light of recent discoveries. Biochem Pharmacol. 2000;59:13–23.
  25. Bowie AG, Moynagh PN, O’Neill LA. Lipid peroxidation is involved in the activation of NF-kappaB by tumor necrosis factor but not interleukin-1 in the human endothelial cell line ECV304. Lack of involvement of H2O2 in NF-kappaB activation by either cytokine in both primary and transformed endothelial cells. J Biol Chem. 1997;272:25941–25950.
  26. Li G, Luna C, Qiu J, Epstein DL, Gonzalez P. Targeting of integrin β1 and kinesin 2α by MicroRNA 183. J Biol Chem. 2010;285:5461–5471.
  27. Luna C, Li G, Qiu J, Epstein DL, Gonzalez P. Role of miR-29b on the regulation of the extracellular matrix in human trabecular meshwork cells under chronic oxidative stress. Mol Vis. 2009;15:2488–2497.
  28. Luna C, Guorong LI, Qiu J, Epstein DL, Gonzalez P. MicroRNA-24 regulates the processing of latent TGFβ1 during cyclic mechanical stress in human trabecular meshwork cells through direct targeting of FURIN. J Cell Physiol. 2011;226:1407–1414.