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CREBZF mRNA nanoparticles suppress breast cancer progression through a positive feedback loop boosted by circPAPD4

BACKGROUND: Breast cancer (BC) negatively impacts the health of women worldwide. Circular RNAs (circRNAs) are a group of endogenous RNAs considered essential regulatory factor in BC tumorigenesis and progression. However, the underlying molecular mechanisms of circRNAs remain unclear. METHODS: Expre...

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Autores principales: Zhou, Boxuan, Xue, Jinhua, Wu, Runxin, Meng, Hongyu, Li, Ruixi, Mo, Zhaohong, Zhai, Hang, Chen, Xianyu, Liu, Rongqiang, Lai, Guie, Chen, Xiaohong, Li, Taiyuan, Zheng, Shiyang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10233212/
https://www.ncbi.nlm.nih.gov/pubmed/37264406
http://dx.doi.org/10.1186/s13046-023-02701-5
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author Zhou, Boxuan
Xue, Jinhua
Wu, Runxin
Meng, Hongyu
Li, Ruixi
Mo, Zhaohong
Zhai, Hang
Chen, Xianyu
Liu, Rongqiang
Lai, Guie
Chen, Xiaohong
Li, Taiyuan
Zheng, Shiyang
author_facet Zhou, Boxuan
Xue, Jinhua
Wu, Runxin
Meng, Hongyu
Li, Ruixi
Mo, Zhaohong
Zhai, Hang
Chen, Xianyu
Liu, Rongqiang
Lai, Guie
Chen, Xiaohong
Li, Taiyuan
Zheng, Shiyang
author_sort Zhou, Boxuan
collection PubMed
description BACKGROUND: Breast cancer (BC) negatively impacts the health of women worldwide. Circular RNAs (circRNAs) are a group of endogenous RNAs considered essential regulatory factor in BC tumorigenesis and progression. However, the underlying molecular mechanisms of circRNAs remain unclear. METHODS: Expression levels of circPAPD4, miR-1269a, CREBZF, and ADAR1 in BC cell lines and tissues were measured using bioinformatics analysis, RT-qPCR, ISH, and IHC. Cell proliferation and apoptosis were measured using CCK8, EdU staining, flow cytometry, and TUNEL assays. Pearson correlation analysis, RNA pull-down, dual-luciferase reporter, and co-immunoprecipitation assays were used to explore the correlation among circPAPD4, miR-1269a, CREBZF, STAT3, and ADAR1. Effects of circPAPD4 overexpression on tumor progression were investigated using in vivo assays. Moreover, CREBZF mRNA delivered by polymeric nanoparticles (CREBZF-mRNA-NPs) was used to examine application value of our findings. RESULTS: CircPAPD4 expression was low in BC tissues and cells. Functionally, circPAPD4 inhibited proliferation and promoted apoptosis in vitro and in vivo. Mechanistically, circPAPD4 biogenesis was regulated by ADAR1. And circPAPD4 promoted CREBZF expression by competitively binding to miR-1269a. More importantly, CREBZF promoted circPAPD4 expression by suppressing STAT3 dimerization and ADAR1 expression, revealing a novel positive feedback loop that curbed BC progression. Systematic delivery of CREBZF-mRNA-NPs effectively induced CREBZF expression and activated the positive feedback loop of circPAPD4/miR-1269a/CREBZF/STAT3/ADAR1, which might suppress BC progression in vitro and in vivo. CONCLUSION: Our findings firstly illustrated that circPAPD4/miR-1269a/CREBZF/STAT3/ADAR1 positive feedback loop mediated BC progression, and delivering CREBZF mRNA nanoparticles suppressed BC progression in vitro and in vivo, which might provide novel insights into therapeutic strategies for breast cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13046-023-02701-5.
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spelling pubmed-102332122023-06-01 CREBZF mRNA nanoparticles suppress breast cancer progression through a positive feedback loop boosted by circPAPD4 Zhou, Boxuan Xue, Jinhua Wu, Runxin Meng, Hongyu Li, Ruixi Mo, Zhaohong Zhai, Hang Chen, Xianyu Liu, Rongqiang Lai, Guie Chen, Xiaohong Li, Taiyuan Zheng, Shiyang J Exp Clin Cancer Res Research BACKGROUND: Breast cancer (BC) negatively impacts the health of women worldwide. Circular RNAs (circRNAs) are a group of endogenous RNAs considered essential regulatory factor in BC tumorigenesis and progression. However, the underlying molecular mechanisms of circRNAs remain unclear. METHODS: Expression levels of circPAPD4, miR-1269a, CREBZF, and ADAR1 in BC cell lines and tissues were measured using bioinformatics analysis, RT-qPCR, ISH, and IHC. Cell proliferation and apoptosis were measured using CCK8, EdU staining, flow cytometry, and TUNEL assays. Pearson correlation analysis, RNA pull-down, dual-luciferase reporter, and co-immunoprecipitation assays were used to explore the correlation among circPAPD4, miR-1269a, CREBZF, STAT3, and ADAR1. Effects of circPAPD4 overexpression on tumor progression were investigated using in vivo assays. Moreover, CREBZF mRNA delivered by polymeric nanoparticles (CREBZF-mRNA-NPs) was used to examine application value of our findings. RESULTS: CircPAPD4 expression was low in BC tissues and cells. Functionally, circPAPD4 inhibited proliferation and promoted apoptosis in vitro and in vivo. Mechanistically, circPAPD4 biogenesis was regulated by ADAR1. And circPAPD4 promoted CREBZF expression by competitively binding to miR-1269a. More importantly, CREBZF promoted circPAPD4 expression by suppressing STAT3 dimerization and ADAR1 expression, revealing a novel positive feedback loop that curbed BC progression. Systematic delivery of CREBZF-mRNA-NPs effectively induced CREBZF expression and activated the positive feedback loop of circPAPD4/miR-1269a/CREBZF/STAT3/ADAR1, which might suppress BC progression in vitro and in vivo. CONCLUSION: Our findings firstly illustrated that circPAPD4/miR-1269a/CREBZF/STAT3/ADAR1 positive feedback loop mediated BC progression, and delivering CREBZF mRNA nanoparticles suppressed BC progression in vitro and in vivo, which might provide novel insights into therapeutic strategies for breast cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13046-023-02701-5. BioMed Central 2023-06-01 /pmc/articles/PMC10233212/ /pubmed/37264406 http://dx.doi.org/10.1186/s13046-023-02701-5 Text en © The Author(s) 2023, corrected publication 2023 https://creativecommons.org/licenses/by/4.0/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 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
Zhou, Boxuan
Xue, Jinhua
Wu, Runxin
Meng, Hongyu
Li, Ruixi
Mo, Zhaohong
Zhai, Hang
Chen, Xianyu
Liu, Rongqiang
Lai, Guie
Chen, Xiaohong
Li, Taiyuan
Zheng, Shiyang
CREBZF mRNA nanoparticles suppress breast cancer progression through a positive feedback loop boosted by circPAPD4
title CREBZF mRNA nanoparticles suppress breast cancer progression through a positive feedback loop boosted by circPAPD4
title_full CREBZF mRNA nanoparticles suppress breast cancer progression through a positive feedback loop boosted by circPAPD4
title_fullStr CREBZF mRNA nanoparticles suppress breast cancer progression through a positive feedback loop boosted by circPAPD4
title_full_unstemmed CREBZF mRNA nanoparticles suppress breast cancer progression through a positive feedback loop boosted by circPAPD4
title_short CREBZF mRNA nanoparticles suppress breast cancer progression through a positive feedback loop boosted by circPAPD4
title_sort crebzf mrna nanoparticles suppress breast cancer progression through a positive feedback loop boosted by circpapd4
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10233212/
https://www.ncbi.nlm.nih.gov/pubmed/37264406
http://dx.doi.org/10.1186/s13046-023-02701-5
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