Hsa_circRNA_000166 accelerates breast cancer progression via the regulation of the miR-326/ELK1 and miR-330-5p/ELK1 axes

PurposesTo probe the expression, clinical significance, roles, and molecular mechanisms of circRNA_000166 in breast cancer (BC).MethodsClinical tissue samples were gathered from 84 BC patients who underwent surgery at the Affiliated Hospital of Chengde Medical College. Clinical data were obtained from medical records and postoperative follow-up. Expression levels of circRNA_000166, miR-326, miR-330-5p, and ELK1 mRNA in BC tissues and cells were measured by qRT-PCR, and ELK1 protein levels were assessed by WB. Pearson's correlation analysis evaluated the interrelationships between these RNAs in clinical samples. Luciferase reporter assays verified the interactions between miR-326/miR-330-5p and circRNA_000166, as well as between miR-326/miR-330-5p and ELK1. Cell proliferation, migration, and apoptosis were examined using CCK-8, colony formation, transwell, and flow cytometry assays, respectively.ResultsCircRNA_000166 was highly expressed in BC tissues and inversely correlated with miR-326/miR-330-5p levels but positively with ELK1 mRNA levels. ELK1 mRNA also inversely associated with miR-326/miR-330-5p levels in BC tissues. Importantly, our findings demonstrated that circRNA_000166 targets miR-326 and miR-330-5p, while ELK1 is the target of miR-326 and miR-330-5p in BC cells. CircRNA_000166 levels positively correlated with tumour size, TNM stage, histological grade, and lymph node metastasis, and negatively associated with postoperative progression-free survival (PFS) and overall survival (OS) in BC patients. CircRNA_000166 was also highly expressed in BC cells, and knockdown of circRNA_000166 reduced proliferation and migration, and increased apoptosis via miR-326/ELK1 and miR-330-5p/ELK1 pathways in vitro.ConclusionCircRNA_000166 enhances BC progression through miR-326/ELK1 and miR-330-5p/ELK1 pathways and shows potential as a biomarker for BC diagnosis and treatment.