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Differential expression of microRNAs contributed to the health efficacy of EGCG in in vitro subarachnoid hemorrhage model

Abstract

(-)-Epigallocatechin-3-gallate (EGCG) exhibited a broader spectrum health efficacy in subarachnoid hemorrhage (SAH) therapy, the mechanisms, however, are largely unknown. Given that miRNAs play important roles in regulation of thousands of genes expression, the effect of EGCG on the expression of miRNAs was investigated to explore the multi-targeting actions of EGCG by using in vitro SAH model. MTT and Western Blot assay was used to assess the health effects of EGCG in SAH progression, and the results showed that oxyhemoglobin (OxyHb)-induced cell proliferation and excessive autophagic activation were significantly inhibited by 50 μM EGCG, but not 1 μM EGCG. By high throughput sequencing analysis, the miRNAs profiles between normal, SAH and EGCG (1 and 50 μM) groups were compared, and a total of 953 miRNAs were identified. Of 192 differentially expressed miRNAs, 43 miRNAs were significantly differentially expressed in SAH (p < 0.01). However, EGCG significantly increased the number of differential expression of miRNAs, which showed 144 and 138 miRNAs (112 and 115 upregulated, 32 and 23 downregulated, p < 0.01) in 1 and 50 μM EGCG groups, respectively. Among all the differentially expressed miRNAs, 13 miRNAs shared by the three groups. 5 miRNAs (miR-218-5p, miR-218b, miR-143-3p, miR-101a-3p, miR-30a-3p) found in both SAH and EGCG 1 μM groups, and 104 miRNAs shared by EGCG 1 μM and EGCG 50 μM groups. Only 1 miRNAs (miR-532-5p) was discovered both in SAH and EGCG 50 μM groups. Besides, 24, 22 and 20 specific differentially expressed miRNAs were discovered in SAH, 1 and 50 μM EGCG groups, respectively. Predicted target genes of differentially expressed miRNAs showed that the most impacted MAPK signaling pathway, especially the upregulated p38 expression in SAH group, was restored to normal level in both EGCG groups, but calcium signaling pathway was enriched only in EGCG 50 μM group. These results revealed that differential expression of miRNAs is fundamental to understand the multiple targets actions of EGCG in SAH therapy, and simultaneously targeting more robust signaling pathways might determine the therapeutic effects of EGCG.

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Publication details

The article was received on 18 Jul 2017, accepted on 06 Nov 2017 and first published on 07 Nov 2017


Article type: Paper
DOI: 10.1039/C7FO01064H
Citation: Food Funct., 2017, Accepted Manuscript
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    Differential expression of microRNAs contributed to the health efficacy of EGCG in in vitro subarachnoid hemorrhage model

    Y. Chen, L. Huang, L. Wang, L. Chen, W. Ren and W. Zhou, Food Funct., 2017, Accepted Manuscript , DOI: 10.1039/C7FO01064H

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