Carcinogenesis, Teratogenesis & Mutagenesis ›› 2025, Vol. 37 ›› Issue (1): 39-44,51.doi: 10.3969/j.issn.1004-616x.2025.01.007

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The role of circular RNA homeodomain interacting protein kinase 3 in triple-negative breast cancer cell invasion

Lü Jie1,2, CHEN Zhonghua1,2, WANG Bo1   

  1. 1. School of Clinical Medicine, Jiamusi University, Jiamusi 154002;
    2. Jiamusi Tumor Hospital, Jiamusi 154002, Heilongjiang, China
  • Received:2023-12-08 Revised:2024-09-14 Published:2025-01-25

Abstract: OBJECTIVE: To investigate the role of circular RNA homeodomain interacting protein kinase 3 (circHIPK3) in triple-negative breast cancer (TNBC) cell invasion. METHODS: From January 2022 to June 2023,40 cases of surgically removed TNBC tissues,40 cases of non-triple negative breast cancer tissues and 40 cases of corresponding paracancer tissues were collected. Expression level of circHIPK3 was detected by fluorescence quantitative PCR. Normal human mammary epithelial cell lines MCF10A,non-triple negative breast cancer cell lines MCF-7 and SK-BR-3,TNBC cell lines HCC1806,MDA-MB-231 and HCC-70 were cultured.,Their expression levels of circHIPK3 were detected by fluorescence quantitative PCR. According to the expression level,MDA-MB-231 cells with the highest circHIPK3 expression were selected for grouping. The siRNA sequence with the most significant circHIPK3 knockdown effect was screened,and then circHIPK3 siRNA and miR-485-3 were co-transfected into MDA-MB-231 cells. Expressions of circHIPK3 and miR-485-3p were detected by fluorescence quantitative PCR. Protein expression of FGF2 was detected by western blot. The number of cell invasions was detected by the transwell invasion assay. RESULTS: The relative expression levels of circHIPK3 in breast cancer tissues were higher than that in adjacent tissues (P<0.05). The relative expression level of circHIPK3 in TNBC tissues was higher than that in non-triple negative breast cancer tissues (P<0.05). The relative expression level of circHIPK3 in TNBC cell lines was higher than that in non-triple negative breast cancer cell lines and normal breast cancer epithelial cell lines (P<0.05),and the expression level of circHIPK3 in MDA-MB-231 cells was higher than that in HCC1806 and HCC-70 cells (P<0.05). Compared with the cells transfected with control siRNA sequence,the expression levels of circHIPK3 and FGF2 and the number of cell invasion in MDA-MB-231 cells transfected with circHIPK3 siRNA were decreased,and the expression level of miR-485-3p was increased (P<0.05). Compared with cells transfected with miRNA control sequences,the expression level of miR-485-3p in MDA-MB-231 cells transfected with miR-485-3p (co-transfected with circHIPK3 siRNA) was decreased,and the expression level of FGF2 and the number of cell invasion were increased (P<0.05). CONCLUSION: CircHIPK3 promoted TNBC cell invasion and a possible mechanism is via promotion of the FGF2 protein expression by inhibiting the expression of miR-485-3p.

Key words: triple-negative breast cancer, circHIPK3, fibroblast growth factor 2, cell invasion

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