Hsa_circ_0007823 Overexpression Suppresses the Progression of Triple-Negative Breast Cancer via Regulating miR-182-5p-FOXO1 Axis

Abstract

Background

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

Abbreviations

qRT-PCR, quantitative real time-PCR, TNBC, triple-negative breast cancer; circRNA, circular RNA; FOXO, forkhead box O; NC, negative control; CCK-8, cell counting kit-8; Rluc, renilla luciferase; OS, overall survival; DFS, disease-free survival; miRNA, microRNA.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This study was supported by Health Industry Clinical Research Project of Shanghai Municipal Health Commission (No.202040144).