Circ-0007766 acts as a miR-1972 sponge to promote breast cancer cell migration and invasion via upregulation of HER2

Background and purpose: Human epidermal growth factor receptor 2 (HER2) serves as one of the paramount drivers of breast cancer metastasis, with roughly 20%-30% of breast cancer patients exhibiting high expression of HER2. The expression level of HER2 is regulatable at multiple molecular levels and determines the metastatic potential of breast cancer cells; however, the manner in which HER2 expression is modulated at the mRNA level remains ambiguous. Circ-0007766 is a circRNA originated from the coding gene ERBB2 for HER2, and whether circ-0007766 can regulate HER2 expression via the ceRNA mechanism has not been reported. This study aimed to analyze whether circ-0007766 acts as a miR-1972 sponge to promote breast cancer cell migration and invasion via upregulation of HER2 expression. Methods: In this study, a high-throughput circRNA chip was employed to screen for circRNAs that exhibited highly specific expression in HER2-positive breast cancer cells. RNA fluorescence in situ hybridization (FISH) was utilized to detect the subcellular localization of circ-0007766. The BaseScope experiment was conducted to analyze the expression level of circ-0007766 in breast cancer tissues and its clinical diagnostic significance. Breast cancer cell models with overexpression and knockdown of circ-0007766 were constructed by transfecting cloning plasmids and siRNA in vitro. The effect of circ-0007766 on the migration and invasion of breast cancer cells was assessed using transwell migration and invasion experiments, and the migration and invasion abilities of MDA-MB-231 and SK-BR-3 cells were measured. Additionally, it was evaluated whether circ-0007766 could promote the migration and invasion of breast cancer cells through miR-1972. A dual luciferase reporter gene assay was used to verify whether circ-0007766 could regulate HER2 expression by binding to miR-1972. The direct interaction between circ-0007766 and miR-1972 was further verified through the RAP experiment. RIP detection was performed in MDA-MB-231 cells, and the relative 3'UTR of HER2 mRNA was measured by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR). Western blot was used to detect the protein expressions. Results: Circ-0007766 was conspicuously highly expressed in HER2-positive breast cancer cells and distributed in both the cytoplasm and nucleus of cells, with the preponderance being in the cytoplasm. The expression level of circ-0007766 was strikingly higher in breast cancer tiss