Yu Jinling, Wang Haofeng, Shen Weida, Zhou Yingzi, Cui Jing, Li Haichuan, Gao Beimin
Department of Breast Surgery, Shanghai Changning Maternity and Infant Health Hospital, East China Normal University, Shanghai, 200050, People's Republic of China.
Department of Pathology, Shanghai Changning Maternity and Infant Health Hospital, East China Normal University, Shanghai, 200050, People's Republic of China.
Breast Cancer (Dove Med Press). 2023 Oct 18;15:695-708. doi: 10.2147/BCTT.S417547. eCollection 2023.
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.
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.
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.
Hsa_circ_0007823 overexpression could suppress the growth, invasion, and migration of TNBC cells, and inhibit tumor growth by regulating miR-182-5p/FOXO1.
本研究旨在分析hsa_circ_0007823在三阴性乳腺癌(TNBC)中的特异性表达,并探讨hsa_circ_0007823在TNBC中的作用及相关分子机制。
采用逆转录-定量聚合酶链反应检测TNBC组织和细胞系中hsa_circ_0007823的相对水平。评估hsa_circ_0007823水平在患者临床病理特征和预后预测中的价值。采用双荧光素酶报告基因测定法确定hsa_circ_0007823、miR-182-5p和FOXO1之间的关系。在体外和体内研究circ_0007823过表达对TNBC细胞生长的影响。
在TNBC组织和细胞系中发现hsa_circ_0007823水平较低,且与淋巴结转移、较差的总生存率和无病生存率密切相关。在TNBC细胞系中,miR-182-5p显著上调,而FOXO1下调。miR-182-5p抑制可上调TNBC细胞中的FOXO1。双荧光素酶报告基因测定显示hsa_circ_0007823、miR-182-5p和FOXO1相互作用。circ_0007823过表达显著抑制TNBC细胞系的活力、迁移和侵袭,但促进凋亡。体内实验表明,circ_0007823过表达抑制肿瘤生长,下调miR-182-5p并上调FOXO1。
hsa_circ_0007823过表达可抑制TNBC细胞的生长、侵袭和迁移,并通过调节miR-182-5p/FOXO1抑制肿瘤生长。