CircRNA75 and CircRNA72 Function as the Sponge of MicroRNA-200 to Suppress Coelomocyte Apoptosis Via Targeting Tollip in Apostichopus japonicus

Circular RNAs (circRNAs) act as essential regulators in many biological processes, especially in mammalian immune response. Nonetheless, the functions and mechanisms of circRNAs in the invertebrate immune system are largely unclarified. In our previous work, 261 differentially expressed circRNAs pot...

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Autores principales: Jiqing Liu, Xuelin Zhao, Xuemei Duan, Weiwei Zhang, Chenghua Li
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:171c5b89da9b42ceb4ffeff0d35d1a572021-11-17T04:49:46ZCircRNA75 and CircRNA72 Function as the Sponge of MicroRNA-200 to Suppress Coelomocyte Apoptosis Via Targeting Tollip in Apostichopus japonicus1664-322410.3389/fimmu.2021.770055https://doaj.org/article/171c5b89da9b42ceb4ffeff0d35d1a572021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.770055/fullhttps://doaj.org/toc/1664-3224Circular RNAs (circRNAs) act as essential regulators in many biological processes, especially in mammalian immune response. Nonetheless, the functions and mechanisms of circRNAs in the invertebrate immune system are largely unclarified. In our previous work, 261 differentially expressed circRNAs potentially related to the development of Apostichopus japonicus skin ulceration syndrome (SUS), which is a major problem restricting the sea cucumber breeding industry, were identified by genome-wide screening. In this study, via miRanda analysis, both circRNA75 and circrRNA72 were shown to share the miR-200 binding site, a key microRNA in the SUS. The two circRNAs were verified to be increased significantly in LPS-exposed primary coelomocytes, similar to the results of circRNA-seq in sea cucumber under Vibrio splendidus-challenged conditions. A dual-luciferase assay indicated that both circRNA75 and circRNA72 could bind miR-200 in vivo, in which circRNA75 had four binding sites of miR-200 and only one for circRNA72. Furthermore, we found that miR-200 could bind the 3’-UTR of Toll interacting protein (Tollip) to negatively mediate the expression of Tollip. Silencing Tollip increased primary coelomocyte apoptosis. Consistently, inference of circRNA75 and circRNA72 could also downregulate Tollip expression, thereby increasing the apoptosis of primary coelomocytes, which could be blocked by miR-200 inhibitor treatment. Moreover, the rate of si-circRNA75-downregulated Tollip expression was higher than that of si-circRNA72 under an equivalent amount. CircRNA75 and circRNA72 suppressed coelomocyte apoptosis by sponging miR-200 to promote Tollip expression. The ability of circRNA to adsorb miRNA might be positively related to the number of binding sites for miRNA.Jiqing LiuJiqing LiuXuelin ZhaoXuelin ZhaoXuemei DuanXuemei DuanWeiwei ZhangWeiwei ZhangChenghua LiChenghua LiChenghua LiFrontiers Media S.A.articleApostichopus japonicuscircRNAmiR-200TollipapoptosisImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Apostichopus japonicus
circRNA
miR-200
Tollip
apoptosis
Immunologic diseases. Allergy
RC581-607
spellingShingle Apostichopus japonicus
circRNA
miR-200
Tollip
apoptosis
Immunologic diseases. Allergy
RC581-607
Jiqing Liu
Jiqing Liu
Xuelin Zhao
Xuelin Zhao
Xuemei Duan
Xuemei Duan
Weiwei Zhang
Weiwei Zhang
Chenghua Li
Chenghua Li
Chenghua Li
CircRNA75 and CircRNA72 Function as the Sponge of MicroRNA-200 to Suppress Coelomocyte Apoptosis Via Targeting Tollip in Apostichopus japonicus
description Circular RNAs (circRNAs) act as essential regulators in many biological processes, especially in mammalian immune response. Nonetheless, the functions and mechanisms of circRNAs in the invertebrate immune system are largely unclarified. In our previous work, 261 differentially expressed circRNAs potentially related to the development of Apostichopus japonicus skin ulceration syndrome (SUS), which is a major problem restricting the sea cucumber breeding industry, were identified by genome-wide screening. In this study, via miRanda analysis, both circRNA75 and circrRNA72 were shown to share the miR-200 binding site, a key microRNA in the SUS. The two circRNAs were verified to be increased significantly in LPS-exposed primary coelomocytes, similar to the results of circRNA-seq in sea cucumber under Vibrio splendidus-challenged conditions. A dual-luciferase assay indicated that both circRNA75 and circRNA72 could bind miR-200 in vivo, in which circRNA75 had four binding sites of miR-200 and only one for circRNA72. Furthermore, we found that miR-200 could bind the 3’-UTR of Toll interacting protein (Tollip) to negatively mediate the expression of Tollip. Silencing Tollip increased primary coelomocyte apoptosis. Consistently, inference of circRNA75 and circRNA72 could also downregulate Tollip expression, thereby increasing the apoptosis of primary coelomocytes, which could be blocked by miR-200 inhibitor treatment. Moreover, the rate of si-circRNA75-downregulated Tollip expression was higher than that of si-circRNA72 under an equivalent amount. CircRNA75 and circRNA72 suppressed coelomocyte apoptosis by sponging miR-200 to promote Tollip expression. The ability of circRNA to adsorb miRNA might be positively related to the number of binding sites for miRNA.
format article
author Jiqing Liu
Jiqing Liu
Xuelin Zhao
Xuelin Zhao
Xuemei Duan
Xuemei Duan
Weiwei Zhang
Weiwei Zhang
Chenghua Li
Chenghua Li
Chenghua Li
author_facet Jiqing Liu
Jiqing Liu
Xuelin Zhao
Xuelin Zhao
Xuemei Duan
Xuemei Duan
Weiwei Zhang
Weiwei Zhang
Chenghua Li
Chenghua Li
Chenghua Li
author_sort Jiqing Liu
title CircRNA75 and CircRNA72 Function as the Sponge of MicroRNA-200 to Suppress Coelomocyte Apoptosis Via Targeting Tollip in Apostichopus japonicus
title_short CircRNA75 and CircRNA72 Function as the Sponge of MicroRNA-200 to Suppress Coelomocyte Apoptosis Via Targeting Tollip in Apostichopus japonicus
title_full CircRNA75 and CircRNA72 Function as the Sponge of MicroRNA-200 to Suppress Coelomocyte Apoptosis Via Targeting Tollip in Apostichopus japonicus
title_fullStr CircRNA75 and CircRNA72 Function as the Sponge of MicroRNA-200 to Suppress Coelomocyte Apoptosis Via Targeting Tollip in Apostichopus japonicus
title_full_unstemmed CircRNA75 and CircRNA72 Function as the Sponge of MicroRNA-200 to Suppress Coelomocyte Apoptosis Via Targeting Tollip in Apostichopus japonicus
title_sort circrna75 and circrna72 function as the sponge of microrna-200 to suppress coelomocyte apoptosis via targeting tollip in apostichopus japonicus
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/171c5b89da9b42ceb4ffeff0d35d1a57
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