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. 2019 May 24;27(1):176–191. doi: 10.1038/s41418-019-0351-4

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© ADMC Associazione Differenziamento e Morte Cellulare 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — H19 competed with PDCD4 for miR-21 to form ceRNET. a Sketch of the dysregulated transcriptome and their correlations. From outside in: chromosome position, lncRNAs in the I/R retina, lncRNAs in the healthy control, miRNAs in the I/R group, miRNAs in the control group, mRNAs in the I/R retina, mRNAs in the healthy control, and interactions among these three types of RNAs in the dysregulated transcriptome. b In cultured microglia, PDCD4 expression was up-regulated by oH19 and the miR-21 inhibitor, and down-regulated by dH19 and the miR-21 mimic. PDCD4 dysregulation was aggravated by simultaneous H19 and miR-21 treatment at transcriptional level. c, d As measured by flow cytometry and ELISA, H19 excision-mediated prevention of IL-1β and IL-18 overproduction was abolished by PDCD4 overexpression in microglia. e As measured by real-time PCR, PDCD4 competed with H19 in regulating the NLRP3/NLRP6 inflammasome balance in microglia. And the expression of caspase-1, GSDMD, and the pro-inflammatory cytokines was increased by PDCD4 overexpression. Data were represented as means ± SD (n = 6). Compared with the OGD/R group: *P < 0.05, **P < 0.01. Compared with dH19 microglia: ^#P < 0.05, ^##P < 0.01. Compared with oH19 microglia: ^$$P < 0.01. NC, normal control lentivirus; dH19, H19 knockout; oH19, H19 overexpression; oPDCD4, PDCD4 overexpression