CircGFRA1 facilitates the malignant progression of HER‐2‐positive breast cancer via acting as a sponge of miR‐1228 and enhancing AIFM2 expression

• Published in: Journal of cellular and molecular medicine Vol. 25; no. 21; pp. 10248 - 10256
• Main Authors: Bazhabayi, Meiheban, Qiu, Xingsheng, Li, Xing, Yang, Anli, Wen, Wei, Zhang, Xiaoli, Xiao, Xiangsheng, He, Rongfang, Liu, Peng
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.11.2021; John Wiley and Sons Inc
• Subjects: AIFM2; Animals; Apoptosis - genetics; Apoptosis Regulatory Proteins - genetics; Biomarkers, Tumor; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell growth; Cell Line, Tumor; Cell proliferation; circGFRA1; Circular RNA; Disease Models, Animal; DNA microarrays; Female; Ferroptosis; Gene Expression Regulation, Neoplastic; Gene Silencing; Glial Cell Line-Derived Neurotrophic Factor Receptors - genetics; HER‐2‐positive breast cancer; Humans; Lungs; Mice; MicroRNAs; MicroRNAs - genetics; miR‐1228; Mitochondrial Proteins - genetics; Original; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; RNA Interference; RNA, Circular - genetics; Tumors; United States > US; China; miR-1228; ferroptosis; HER-2-positive breast cancer; AIFM2; circGFRA1
• ISSN: 1582-1838; 1582-4934; 1582-4934
• DOI: 10.1111/jcmm.16963

CircRNAs (circular RNA) are reported to regulate onset and progress multiple cancers. Nonetheless, the function along with the underlying mechanisms of circRNAs in HER‐2‐positive breast cancer (BC) remains unclear. CircRNA microarrays were performed to elucidate expression profiles of HER‐2‐positive BC cells. circRNA levels were quantified using qRT‐PCR assay. Various in vitro along with in vivo assays were employed to further explore the effects of circGFRA1 in the progress of HER‐2‐positive BC and interactions of circGFRA1, miR‐1228 and AIFM2 in Her‐2‐positive BC. CircGFRA1 was remarkably upregulated in HER‐2‐positive BC. Knockdown of circGFRA1 could attenuate HER‐2‐positive BC progression by inhibiting the proliferation, infiltration and migratory ability of HER‐2‐positive BC cells. Through ceRNA mechanism, circGFRA1 could bind to miR‐1228 and alleviate inhibitory activity of miR‐1228 on targeted gene AIFM2. In summary, circGFRA1‐miR‐1228‐AIFM2 axis regulates HER‐2‐positive BC. CircGFRA1 is a novel promising treatment option for HER‐2‐positive BC.