Oncogenic hsa_circ_0000247 Promotes Breast Cancer Malignancy Through hsa‐let‐7i‐5p Sponging‐Mediated HMGA1 Upregulation

ABSTRACT

Circular RNAs (circRNAs) are stable, evolutionarily conserved non‐coding RNAs with covalently closed‐loop structures, which function as oncogenes or tumor suppressors to regulate cancer cell proliferation, invasion, metastasis, and apoptosis. This study explored the role and regulatory mechanism of hsa_circ_0000247 in breast cancer. The expression levels of hsa_circ_0000247, hsa‐let‐7i‐5p, and HMGA1 were detected by RT‐qPCR and western blotting. Biological functions were evaluated using CCK‐8, EdU, colony formation, Transwell, flow cytometry, and electron microscopy assays. The interactions among hsa_circ_0000247, hsa‐let‐7i‐5p, and HMGA1 were verified by dual‐luciferase reporter assays, and rescue experiments were conducted. Hsa_circ_0000247 was significantly upregulated in 30 pairs of breast cancer tissues and MCF‐7, MDA‐MB‐231, and BT‐474 cell lines. Knockdown of hsa_circ_0000247 inhibited cell proliferation, migration, and invasion, and promoted apoptosis. Mechanistically, hsa_circ_0000247 directly sponged hsa‐let‐7i‐5p, which targeted the 3′UTR of HMGA1. Inhibition of hsa‐let‐7i‐5p reversed the effects of hsa_circ_0000247 silencing. In conclusion, hsa_circ_0000247 is upregulated in breast cancer and promotes malignant progression via the hsa_circ_0000247/hsa‐let‐7i‐5p/HMGA1 axis, providing a potential diagnostic and therapeutic target for breast cancer.