Cargando…

Circular RNA circ_IRAK3 contributes to tumor growth through upregulating KIF2A via adsorbing miR-603 in breast cancer

BACKGROUND: Breast cancer (BC) threatens the health of women around the world. Researchers have proved that hsa_circ_0005505 (circ_IRAK3) facilitates BC cell invasion and migration, but the regulatory mechanisms of circ_IRAK3 in BC remain mostly unknown. We aim to explore a new mechanism by which ci...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Fang, Li, Jingruo, Li, Lin, Chen, Zhuo, Wang, Nan, Zhu, Mingzhi, Mi, Hailong, Xiong, Youyi, Guo, Guangcheng, Gu, Yuanting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8845402/
https://www.ncbi.nlm.nih.gov/pubmed/35164763
http://dx.doi.org/10.1186/s12935-022-02497-y
_version_ 1784651669432172544
author Wang, Fang
Li, Jingruo
Li, Lin
Chen, Zhuo
Wang, Nan
Zhu, Mingzhi
Mi, Hailong
Xiong, Youyi
Guo, Guangcheng
Gu, Yuanting
author_facet Wang, Fang
Li, Jingruo
Li, Lin
Chen, Zhuo
Wang, Nan
Zhu, Mingzhi
Mi, Hailong
Xiong, Youyi
Guo, Guangcheng
Gu, Yuanting
author_sort Wang, Fang
collection PubMed
description BACKGROUND: Breast cancer (BC) threatens the health of women around the world. Researchers have proved that hsa_circ_0005505 (circ_IRAK3) facilitates BC cell invasion and migration, but the regulatory mechanisms of circ_IRAK3 in BC remain mostly unknown. We aim to explore a new mechanism by which circ_IRAK3 promotes BC progression. METHODS: Levels of circ_IRAK3, microRNA (miR)-603, and kinesin family member 2A (KIF2A) mRNA in BC tissues and cells were examined by quantitative real-time polymerase chain reaction (qRT-PCR). The cell cycle progression, colony formation, and proliferation of BC cells were evaluated by flow cytometry, plate clone, or 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assays. The migration, invasion, and apoptosis of BC cells were determined by transwell or flow cytometry assays. Several protein levels were detected using western blotting. The targeting relationship between circ_IRAK3 or KIF2A and miR-603 was verified via dual-luciferase reporter assay. The role of circ_IRAK3 in vivo was verified by xenograft assay. RESULTS: We observed higher levels of circ_IRAK3 in BC tissues and cell lines than their respective controls. Functional experiments presented that circ_IRAK3 silencing induced BC cell apoptosis, curbed cell proliferation, migration, and invasion in vitro, and decreased tumor growth in vivo. Mechanistically, circ_IRAK3 could modulate kinesin family member 2A (KIF2A) expression through acting as a microRNA (miR)-603 sponge. miR-603 silencing impaired the effects of circ_IRAK3 inhibition on the malignant behaviors of BC cells. Also, the repressive effects of miR-603 mimic on the malignant behaviors of BC cells were weakened by KIF2A overexpression. CONCLUSIONS: circ_IRAK3 exerted a promoting effect on BC progression by modulating the miR-603/KIF2A axis, providing a piece of novel evidence for circ_IRAK3 as a therapeutic target for BC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-022-02497-y.
format Online
Article
Text
id pubmed-8845402
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-88454022022-02-16 Circular RNA circ_IRAK3 contributes to tumor growth through upregulating KIF2A via adsorbing miR-603 in breast cancer Wang, Fang Li, Jingruo Li, Lin Chen, Zhuo Wang, Nan Zhu, Mingzhi Mi, Hailong Xiong, Youyi Guo, Guangcheng Gu, Yuanting Cancer Cell Int Primary Research BACKGROUND: Breast cancer (BC) threatens the health of women around the world. Researchers have proved that hsa_circ_0005505 (circ_IRAK3) facilitates BC cell invasion and migration, but the regulatory mechanisms of circ_IRAK3 in BC remain mostly unknown. We aim to explore a new mechanism by which circ_IRAK3 promotes BC progression. METHODS: Levels of circ_IRAK3, microRNA (miR)-603, and kinesin family member 2A (KIF2A) mRNA in BC tissues and cells were examined by quantitative real-time polymerase chain reaction (qRT-PCR). The cell cycle progression, colony formation, and proliferation of BC cells were evaluated by flow cytometry, plate clone, or 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assays. The migration, invasion, and apoptosis of BC cells were determined by transwell or flow cytometry assays. Several protein levels were detected using western blotting. The targeting relationship between circ_IRAK3 or KIF2A and miR-603 was verified via dual-luciferase reporter assay. The role of circ_IRAK3 in vivo was verified by xenograft assay. RESULTS: We observed higher levels of circ_IRAK3 in BC tissues and cell lines than their respective controls. Functional experiments presented that circ_IRAK3 silencing induced BC cell apoptosis, curbed cell proliferation, migration, and invasion in vitro, and decreased tumor growth in vivo. Mechanistically, circ_IRAK3 could modulate kinesin family member 2A (KIF2A) expression through acting as a microRNA (miR)-603 sponge. miR-603 silencing impaired the effects of circ_IRAK3 inhibition on the malignant behaviors of BC cells. Also, the repressive effects of miR-603 mimic on the malignant behaviors of BC cells were weakened by KIF2A overexpression. CONCLUSIONS: circ_IRAK3 exerted a promoting effect on BC progression by modulating the miR-603/KIF2A axis, providing a piece of novel evidence for circ_IRAK3 as a therapeutic target for BC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-022-02497-y. BioMed Central 2022-02-14 /pmc/articles/PMC8845402/ /pubmed/35164763 http://dx.doi.org/10.1186/s12935-022-02497-y 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 Primary Research
Wang, Fang
Li, Jingruo
Li, Lin
Chen, Zhuo
Wang, Nan
Zhu, Mingzhi
Mi, Hailong
Xiong, Youyi
Guo, Guangcheng
Gu, Yuanting
Circular RNA circ_IRAK3 contributes to tumor growth through upregulating KIF2A via adsorbing miR-603 in breast cancer
title Circular RNA circ_IRAK3 contributes to tumor growth through upregulating KIF2A via adsorbing miR-603 in breast cancer
title_full Circular RNA circ_IRAK3 contributes to tumor growth through upregulating KIF2A via adsorbing miR-603 in breast cancer
title_fullStr Circular RNA circ_IRAK3 contributes to tumor growth through upregulating KIF2A via adsorbing miR-603 in breast cancer
title_full_unstemmed Circular RNA circ_IRAK3 contributes to tumor growth through upregulating KIF2A via adsorbing miR-603 in breast cancer
title_short Circular RNA circ_IRAK3 contributes to tumor growth through upregulating KIF2A via adsorbing miR-603 in breast cancer
title_sort circular rna circ_irak3 contributes to tumor growth through upregulating kif2a via adsorbing mir-603 in breast cancer
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8845402/
https://www.ncbi.nlm.nih.gov/pubmed/35164763
http://dx.doi.org/10.1186/s12935-022-02497-y
work_keys_str_mv AT wangfang circularrnacircirak3contributestotumorgrowththroughupregulatingkif2aviaadsorbingmir603inbreastcancer
AT lijingruo circularrnacircirak3contributestotumorgrowththroughupregulatingkif2aviaadsorbingmir603inbreastcancer
AT lilin circularrnacircirak3contributestotumorgrowththroughupregulatingkif2aviaadsorbingmir603inbreastcancer
AT chenzhuo circularrnacircirak3contributestotumorgrowththroughupregulatingkif2aviaadsorbingmir603inbreastcancer
AT wangnan circularrnacircirak3contributestotumorgrowththroughupregulatingkif2aviaadsorbingmir603inbreastcancer
AT zhumingzhi circularrnacircirak3contributestotumorgrowththroughupregulatingkif2aviaadsorbingmir603inbreastcancer
AT mihailong circularrnacircirak3contributestotumorgrowththroughupregulatingkif2aviaadsorbingmir603inbreastcancer
AT xiongyouyi circularrnacircirak3contributestotumorgrowththroughupregulatingkif2aviaadsorbingmir603inbreastcancer
AT guoguangcheng circularrnacircirak3contributestotumorgrowththroughupregulatingkif2aviaadsorbingmir603inbreastcancer
AT guyuanting circularrnacircirak3contributestotumorgrowththroughupregulatingkif2aviaadsorbingmir603inbreastcancer