Cargando…

EIF4A3-mediated circ_0042881 activates the RAS pathway via miR-217/SOS1 axis to facilitate breast cancer progression

Breast cancer (BC) is one of the most frequent cancer-related deaths in women worldwide. Studies have shown the potential impact of circRNAs in multiple human tumorigeneses. Research on the vital signaling pathways and therapeutic targets of circRNAs is indispensable. Here, we aimed to investigate t...

Descripción completa

Detalles Bibliográficos
Autores principales: Ju, Chenxi, Zhou, Mingxia, Du, Dan, Wang, Chang, Yao, Jieqiong, Li, Hongle, Luo, Yang, He, Fucheng, He, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10457341/
https://www.ncbi.nlm.nih.gov/pubmed/37626035
http://dx.doi.org/10.1038/s41419-023-06085-4
_version_ 1785096901344886784
author Ju, Chenxi
Zhou, Mingxia
Du, Dan
Wang, Chang
Yao, Jieqiong
Li, Hongle
Luo, Yang
He, Fucheng
He, Jing
author_facet Ju, Chenxi
Zhou, Mingxia
Du, Dan
Wang, Chang
Yao, Jieqiong
Li, Hongle
Luo, Yang
He, Fucheng
He, Jing
author_sort Ju, Chenxi
collection PubMed
description Breast cancer (BC) is one of the most frequent cancer-related deaths in women worldwide. Studies have shown the potential impact of circRNAs in multiple human tumorigeneses. Research on the vital signaling pathways and therapeutic targets of circRNAs is indispensable. Here, we aimed to investigate the clinical implications and underlying mechanisms of circ_0042881 in BC. RT-qPCR validated circ_0042881 was notably elevated in BC tissues and plasma, and closely associated with BC clinicopathological features. Functionally, circ_0042881 significantly accelerated the proliferation, migration, and invasion of BC cells in vitro and tumor growth and metastasis in vivo. Mechanistically, circ_0042881 promoted BC progression by sponging miR-217 to relieve its inhibition effect in son of sevenless 1 (SOS1), which further activated RAS protein and initiated downstream signaling cascades, including MEK/ERK pathway and PI3K/AKT pathway. We also demonstrated that treatment of BAY-293, an inhibitor of SOS1 and RAS interaction, attenuated BC progression induced by circ_0042881 overexpression. Furthermore, Eukaryotic initiation factor 4A-III (EIF4A3) could facilitate circ_0042881 circularization. Altogether, we proposed a novel signaling network in which circ_0042881, induced by EIF4A3, influences the process of BC tumorigenesis and metastasis by miR-217/SOS1 axis.
format Online
Article
Text
id pubmed-10457341
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-104573412023-08-27 EIF4A3-mediated circ_0042881 activates the RAS pathway via miR-217/SOS1 axis to facilitate breast cancer progression Ju, Chenxi Zhou, Mingxia Du, Dan Wang, Chang Yao, Jieqiong Li, Hongle Luo, Yang He, Fucheng He, Jing Cell Death Dis Article Breast cancer (BC) is one of the most frequent cancer-related deaths in women worldwide. Studies have shown the potential impact of circRNAs in multiple human tumorigeneses. Research on the vital signaling pathways and therapeutic targets of circRNAs is indispensable. Here, we aimed to investigate the clinical implications and underlying mechanisms of circ_0042881 in BC. RT-qPCR validated circ_0042881 was notably elevated in BC tissues and plasma, and closely associated with BC clinicopathological features. Functionally, circ_0042881 significantly accelerated the proliferation, migration, and invasion of BC cells in vitro and tumor growth and metastasis in vivo. Mechanistically, circ_0042881 promoted BC progression by sponging miR-217 to relieve its inhibition effect in son of sevenless 1 (SOS1), which further activated RAS protein and initiated downstream signaling cascades, including MEK/ERK pathway and PI3K/AKT pathway. We also demonstrated that treatment of BAY-293, an inhibitor of SOS1 and RAS interaction, attenuated BC progression induced by circ_0042881 overexpression. Furthermore, Eukaryotic initiation factor 4A-III (EIF4A3) could facilitate circ_0042881 circularization. Altogether, we proposed a novel signaling network in which circ_0042881, induced by EIF4A3, influences the process of BC tumorigenesis and metastasis by miR-217/SOS1 axis. Nature Publishing Group UK 2023-08-25 /pmc/articles/PMC10457341/ /pubmed/37626035 http://dx.doi.org/10.1038/s41419-023-06085-4 Text en © The Author(s) 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Ju, Chenxi
Zhou, Mingxia
Du, Dan
Wang, Chang
Yao, Jieqiong
Li, Hongle
Luo, Yang
He, Fucheng
He, Jing
EIF4A3-mediated circ_0042881 activates the RAS pathway via miR-217/SOS1 axis to facilitate breast cancer progression
title EIF4A3-mediated circ_0042881 activates the RAS pathway via miR-217/SOS1 axis to facilitate breast cancer progression
title_full EIF4A3-mediated circ_0042881 activates the RAS pathway via miR-217/SOS1 axis to facilitate breast cancer progression
title_fullStr EIF4A3-mediated circ_0042881 activates the RAS pathway via miR-217/SOS1 axis to facilitate breast cancer progression
title_full_unstemmed EIF4A3-mediated circ_0042881 activates the RAS pathway via miR-217/SOS1 axis to facilitate breast cancer progression
title_short EIF4A3-mediated circ_0042881 activates the RAS pathway via miR-217/SOS1 axis to facilitate breast cancer progression
title_sort eif4a3-mediated circ_0042881 activates the ras pathway via mir-217/sos1 axis to facilitate breast cancer progression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10457341/
https://www.ncbi.nlm.nih.gov/pubmed/37626035
http://dx.doi.org/10.1038/s41419-023-06085-4
work_keys_str_mv AT juchenxi eif4a3mediatedcirc0042881activatestheraspathwayviamir217sos1axistofacilitatebreastcancerprogression
AT zhoumingxia eif4a3mediatedcirc0042881activatestheraspathwayviamir217sos1axistofacilitatebreastcancerprogression
AT dudan eif4a3mediatedcirc0042881activatestheraspathwayviamir217sos1axistofacilitatebreastcancerprogression
AT wangchang eif4a3mediatedcirc0042881activatestheraspathwayviamir217sos1axistofacilitatebreastcancerprogression
AT yaojieqiong eif4a3mediatedcirc0042881activatestheraspathwayviamir217sos1axistofacilitatebreastcancerprogression
AT lihongle eif4a3mediatedcirc0042881activatestheraspathwayviamir217sos1axistofacilitatebreastcancerprogression
AT luoyang eif4a3mediatedcirc0042881activatestheraspathwayviamir217sos1axistofacilitatebreastcancerprogression
AT hefucheng eif4a3mediatedcirc0042881activatestheraspathwayviamir217sos1axistofacilitatebreastcancerprogression
AT hejing eif4a3mediatedcirc0042881activatestheraspathwayviamir217sos1axistofacilitatebreastcancerprogression