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Circ_0119872 promotes uveal melanoma development by regulating the miR-622/G3BP1 axis and downstream signalling pathways

BACKGROUND: The abnormal expression of circular RNAs (circRNAs) in uveal melanoma (UM) has been revealed, but the specific underlying molecular mechanism of their association with UM development has not been fully explored. METHODS: The levels of circ_0119872, G3BP1 and miR-622 in UM cell lines and...

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Autores principales: Liu, Shuting, Chen, Liang, Chen, Hua, Xu, Kangkang, Peng, Xi, Zhang, Mingchang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881613/
https://www.ncbi.nlm.nih.gov/pubmed/33579337
http://dx.doi.org/10.1186/s13046-021-01833-w
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author Liu, Shuting
Chen, Liang
Chen, Hua
Xu, Kangkang
Peng, Xi
Zhang, Mingchang
author_facet Liu, Shuting
Chen, Liang
Chen, Hua
Xu, Kangkang
Peng, Xi
Zhang, Mingchang
author_sort Liu, Shuting
collection PubMed
description BACKGROUND: The abnormal expression of circular RNAs (circRNAs) in uveal melanoma (UM) has been revealed, but the specific underlying molecular mechanism of their association with UM development has not been fully explored. METHODS: The levels of circ_0119872, G3BP1 and miR-622 in UM cell lines and tissues were determined by quantitative real-time PCR (qRT-PCR) and western blotting assays. In vitro and in vivo assays were performed to investigate the function of circ_0119872 in the tumorigenesis of UM cells. The relationships among circ_0119872, miR-622 and G3BP1 were predicted using bioinformatic tools and verified by RNA-FISH, RNA pull-down and dual-luciferase reporter assays. The effects of circ_0119872 on Wnt/β-catenin and mTOR signalling pathways were determined by gene set enrichment analysis (GSEA) and western blotting. RESULTS: We found that circ_0119872 is upregulated in UM cell lines and tissues. Moreover, overexpression of circ_0119872 promotes the malignancy of UM cells, while silencing of circ_0119872 inhibits it. In addition, circ_0119872 can directly interact with miR-622 as a miRNA sponge that regulates the expression of the miR-622 target gene G3BP1 as well as downstream Wnt/β-catenin and mTOR signalling pathways. CONCLUSIONS: Circ_0119872 may act as an oncogene in UM through a novel circ_0119872/miR-622/G3BP1 axis, activating the Wnt/β-catenin and mTOR signalling pathways, which in turn may provide potential biomarkers and therapeutic targets for the management of UM. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13046-021-01833-w.
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spelling pubmed-78816132021-02-17 Circ_0119872 promotes uveal melanoma development by regulating the miR-622/G3BP1 axis and downstream signalling pathways Liu, Shuting Chen, Liang Chen, Hua Xu, Kangkang Peng, Xi Zhang, Mingchang J Exp Clin Cancer Res Research BACKGROUND: The abnormal expression of circular RNAs (circRNAs) in uveal melanoma (UM) has been revealed, but the specific underlying molecular mechanism of their association with UM development has not been fully explored. METHODS: The levels of circ_0119872, G3BP1 and miR-622 in UM cell lines and tissues were determined by quantitative real-time PCR (qRT-PCR) and western blotting assays. In vitro and in vivo assays were performed to investigate the function of circ_0119872 in the tumorigenesis of UM cells. The relationships among circ_0119872, miR-622 and G3BP1 were predicted using bioinformatic tools and verified by RNA-FISH, RNA pull-down and dual-luciferase reporter assays. The effects of circ_0119872 on Wnt/β-catenin and mTOR signalling pathways were determined by gene set enrichment analysis (GSEA) and western blotting. RESULTS: We found that circ_0119872 is upregulated in UM cell lines and tissues. Moreover, overexpression of circ_0119872 promotes the malignancy of UM cells, while silencing of circ_0119872 inhibits it. In addition, circ_0119872 can directly interact with miR-622 as a miRNA sponge that regulates the expression of the miR-622 target gene G3BP1 as well as downstream Wnt/β-catenin and mTOR signalling pathways. CONCLUSIONS: Circ_0119872 may act as an oncogene in UM through a novel circ_0119872/miR-622/G3BP1 axis, activating the Wnt/β-catenin and mTOR signalling pathways, which in turn may provide potential biomarkers and therapeutic targets for the management of UM. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13046-021-01833-w. BioMed Central 2021-02-12 /pmc/articles/PMC7881613/ /pubmed/33579337 http://dx.doi.org/10.1186/s13046-021-01833-w Text en © The Author(s) 2021 Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Liu, Shuting
Chen, Liang
Chen, Hua
Xu, Kangkang
Peng, Xi
Zhang, Mingchang
Circ_0119872 promotes uveal melanoma development by regulating the miR-622/G3BP1 axis and downstream signalling pathways
title Circ_0119872 promotes uveal melanoma development by regulating the miR-622/G3BP1 axis and downstream signalling pathways
title_full Circ_0119872 promotes uveal melanoma development by regulating the miR-622/G3BP1 axis and downstream signalling pathways
title_fullStr Circ_0119872 promotes uveal melanoma development by regulating the miR-622/G3BP1 axis and downstream signalling pathways
title_full_unstemmed Circ_0119872 promotes uveal melanoma development by regulating the miR-622/G3BP1 axis and downstream signalling pathways
title_short Circ_0119872 promotes uveal melanoma development by regulating the miR-622/G3BP1 axis and downstream signalling pathways
title_sort circ_0119872 promotes uveal melanoma development by regulating the mir-622/g3bp1 axis and downstream signalling pathways
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881613/
https://www.ncbi.nlm.nih.gov/pubmed/33579337
http://dx.doi.org/10.1186/s13046-021-01833-w
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