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CircESRP1 enhances metastasis and epithelial–mesenchymal transition in endometrial cancer via the miR-874-3p/CPEB4 axis

BACKGROUND: Metastasis is critical for endometrial cancer (EC) progression and prognosis. Accumulating evidence suggests that circular RNAs (circRNAs) can operate as independent functional entities. However, the functional regulatory mechanisms of circRNAs in EC remain unclear. METHODS: The levels o...

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Autores principales: Shi, Rui, Zhang, Wei, Zhang, Jun, Yu, Zhicheng, An, Lanfen, Zhao, Rong, Zhou, Xing, Wang, Ziwei, Wei, Sitian, Wang, Hongbo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8939068/
https://www.ncbi.nlm.nih.gov/pubmed/35317822
http://dx.doi.org/10.1186/s12967-022-03334-6
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author Shi, Rui
Zhang, Wei
Zhang, Jun
Yu, Zhicheng
An, Lanfen
Zhao, Rong
Zhou, Xing
Wang, Ziwei
Wei, Sitian
Wang, Hongbo
author_facet Shi, Rui
Zhang, Wei
Zhang, Jun
Yu, Zhicheng
An, Lanfen
Zhao, Rong
Zhou, Xing
Wang, Ziwei
Wei, Sitian
Wang, Hongbo
author_sort Shi, Rui
collection PubMed
description BACKGROUND: Metastasis is critical for endometrial cancer (EC) progression and prognosis. Accumulating evidence suggests that circular RNAs (circRNAs) can operate as independent functional entities. However, the functional regulatory mechanisms of circRNAs in EC remain unclear. METHODS: The levels of circESRP1, miR-874-3p, and CPEB4 mRNA in EC tissues and cells were determined by qRT-PCR. Sanger sequencing, PCR with divergent primers, an actinomycin D assay, and RNase R treatment were applied to verify the circular properties. Fluorescence in situ hybridization (FISH) and nuclear-cytoplasmic fractionation were used to determine the localization of circESRP1. CCK-8, EdU incorporation, colony formation, Transwell, and wound healing assays were applied to assess the effects of circESRP1 on cell proliferation, migration, and invasion. The mutual regulatory mechanism of ceRNAs was investigated using dual-luciferase reporter, RNA pulldown, RNA immunoprecipitation (RIP), and Western blot assays. The biological effects were further validated in vivo in nude mouse xenograft models. RESULTS: circESRP1 was highly expressed in EC tissues and cells and was mainly localized in the cytoplasm. Silencing circESRP1 inhibited the proliferation, migration, and invasion of EC cells in vitro and in vivo; however, overexpression of circESRP1 had the opposite effects. Mechanistically, circESRP1 sponged miR-874-3p to upregulate CPEB4 expression and ultimately contribute to EC cell proliferation and metastasis. Furthermore, circESRP1 regulated tumour growth in xenograft models. CONCLUSIONS: CircESRP1 can interact with miR-874-3p to regulate EMT in endometrial cancer via the miR-874-3p/CPEB4 axis. CircESRP1 may serve as a promising therapeutic target for endometrial cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-022-03334-6.
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spelling pubmed-89390682022-03-23 CircESRP1 enhances metastasis and epithelial–mesenchymal transition in endometrial cancer via the miR-874-3p/CPEB4 axis Shi, Rui Zhang, Wei Zhang, Jun Yu, Zhicheng An, Lanfen Zhao, Rong Zhou, Xing Wang, Ziwei Wei, Sitian Wang, Hongbo J Transl Med Research BACKGROUND: Metastasis is critical for endometrial cancer (EC) progression and prognosis. Accumulating evidence suggests that circular RNAs (circRNAs) can operate as independent functional entities. However, the functional regulatory mechanisms of circRNAs in EC remain unclear. METHODS: The levels of circESRP1, miR-874-3p, and CPEB4 mRNA in EC tissues and cells were determined by qRT-PCR. Sanger sequencing, PCR with divergent primers, an actinomycin D assay, and RNase R treatment were applied to verify the circular properties. Fluorescence in situ hybridization (FISH) and nuclear-cytoplasmic fractionation were used to determine the localization of circESRP1. CCK-8, EdU incorporation, colony formation, Transwell, and wound healing assays were applied to assess the effects of circESRP1 on cell proliferation, migration, and invasion. The mutual regulatory mechanism of ceRNAs was investigated using dual-luciferase reporter, RNA pulldown, RNA immunoprecipitation (RIP), and Western blot assays. The biological effects were further validated in vivo in nude mouse xenograft models. RESULTS: circESRP1 was highly expressed in EC tissues and cells and was mainly localized in the cytoplasm. Silencing circESRP1 inhibited the proliferation, migration, and invasion of EC cells in vitro and in vivo; however, overexpression of circESRP1 had the opposite effects. Mechanistically, circESRP1 sponged miR-874-3p to upregulate CPEB4 expression and ultimately contribute to EC cell proliferation and metastasis. Furthermore, circESRP1 regulated tumour growth in xenograft models. CONCLUSIONS: CircESRP1 can interact with miR-874-3p to regulate EMT in endometrial cancer via the miR-874-3p/CPEB4 axis. CircESRP1 may serve as a promising therapeutic target for endometrial cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-022-03334-6. BioMed Central 2022-03-22 /pmc/articles/PMC8939068/ /pubmed/35317822 http://dx.doi.org/10.1186/s12967-022-03334-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/ 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/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://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
Shi, Rui
Zhang, Wei
Zhang, Jun
Yu, Zhicheng
An, Lanfen
Zhao, Rong
Zhou, Xing
Wang, Ziwei
Wei, Sitian
Wang, Hongbo
CircESRP1 enhances metastasis and epithelial–mesenchymal transition in endometrial cancer via the miR-874-3p/CPEB4 axis
title CircESRP1 enhances metastasis and epithelial–mesenchymal transition in endometrial cancer via the miR-874-3p/CPEB4 axis
title_full CircESRP1 enhances metastasis and epithelial–mesenchymal transition in endometrial cancer via the miR-874-3p/CPEB4 axis
title_fullStr CircESRP1 enhances metastasis and epithelial–mesenchymal transition in endometrial cancer via the miR-874-3p/CPEB4 axis
title_full_unstemmed CircESRP1 enhances metastasis and epithelial–mesenchymal transition in endometrial cancer via the miR-874-3p/CPEB4 axis
title_short CircESRP1 enhances metastasis and epithelial–mesenchymal transition in endometrial cancer via the miR-874-3p/CPEB4 axis
title_sort circesrp1 enhances metastasis and epithelial–mesenchymal transition in endometrial cancer via the mir-874-3p/cpeb4 axis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8939068/
https://www.ncbi.nlm.nih.gov/pubmed/35317822
http://dx.doi.org/10.1186/s12967-022-03334-6
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