Abstract
BackgroundBreast 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.MethodsLevels 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.ResultsWe 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.Conclusionscirc_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.
Highlights
Breast cancer (BC) is a complex heterogeneous disease in women, accounting for about 25% of female cancer cases [1, 2]
Through the prediction of the circBank database, we found that circ_IRAK3 may interact with miR-603, which plays a suppressive role in BC [19]
Cell culture BC cells (HCC70 and MDA-MB-231) and human mammary gland epithelial cells (MCF-10A) were bought from the American Type Culture Collection (Manassas, VA, USA). These cells were cultured in mammary epithelial cell growth medium (MEGM) BulletKit (Lonza, Basel, Switzerland) (MCF-10A cells) or Roswell Park Memorial Institute-1640 medium (Sigma, St Louis, MO, USA) (HCC70 and MDA-MB-231) supplemented with 10% fetal bovine serum (FBS) (Sigma) and 1% streptomycin/ penicillin (Solarbio, Beijing, China) and maintained at 37 °C in a moist atmosphere with 5% CO2
Summary
Breast cancer (BC) is a complex heterogeneous disease in women, accounting for about 25% of female cancer cases [1, 2]. BC patients have a good prognosis, but metastatic and chemo-resistant BC patients have a poor prognosis [4]. The mechanism related to the biological behaviors of BC is still unclear, so it is necessary to study new mechanisms to provide latent therapeutic targets [5]. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
