Breast Cancer: Targets and Therapy (Oct 2023)
Hsa_circ_0007823 Overexpression Suppresses the Progression of Triple-Negative Breast Cancer via Regulating miR-182-5p-FOXO1 Axis
Abstract
Jinling Yu,1 Haofeng Wang,1 Weida Shen,1 Yingzi Zhou,2 Jing Cui,1 Haichuan Li,3 Beimin Gao1 1Department of Breast Surgery, Shanghai Changning Maternity and Infant Health Hospital, East China Normal University, Shanghai, 200050, People’s Republic of China; 2Department of Pathology, Shanghai Changning Maternity and Infant Health Hospital, East China Normal University, Shanghai, 200050, People’s Republic of China; 3Department of Laboratory, Shanghai Changning Maternity and Infant Health Hospital, East China Normal University, Shanghai, 200050, People’s Republic of ChinaCorrespondence: Beimin Gao; Haichuan Li, Shanghai Changning Maternity and Infant Health Hospital, East China Normal University, No. 786, Yuyuan Road, Changning District, Shanghai, 200050, People’s Republic of China, Tel +86-21-62288686-2401, Email [email protected]; [email protected]: This study aimed to analyze the specific expression of hsa_circ_0007823 in triple-negative breast cancer (TNBC) and explore the roles and related molecular mechanisms of hsa_circ_0007823 in TNBC.Materials and Methods: Relative hsa_circ_0007823 levels in TNBC tissues and cell lines were examined by reverse transcription-quantitative polymerase chain reaction. The value of hsa_circ_0007823 levels was evaluated in patients’ clinicopathological characteristics and prognostic prediction. A dual-luciferase reporter assay was used to determine the relationship between hsa_circ_0007823, miR-182-5p, and FOXO1. The effect of circ_0007823 overexpression on the growth of TNBC cells was investigated in vitro and in vivo.Results: Lower levels of hsa_circ_0007823 were found in TNBC tissues and cell lines and were closely associated with lymph node metastasis, poorer overall and disease-free survival rates. MiR-182-5p was significantly up-regulated, whereas FOXO1 was down-regulated in TNBC cell lines. The miR-182-5p inhibition up-regulated FOXO1 in TNBC cells. Dual-luciferase reporter assays showed that hsa_circ_0007823, miR-182-5p, and FOXO1 interacted with each other. Overexpression of circ_0007823 significantly inhibited the viability, migration, and invasion of TNBC cell lines, but promoted apoptosis. In vivo experiments showed that circ_0007823 overexpression inhibited tumor growth and down-regulated miR-182-5p and up-regulated FOXO1.Conclusion: Hsa_circ_0007823 overexpression could suppress the growth, invasion, and migration of TNBC cells, and inhibit tumor growth by regulating miR-182-5p/FOXO1.Keywords: triple-negative breast cancer, hsa_circ_0007823, miR-182, FOXO1, biological functional analysis
