Abstract
Breast cancer (BC) is the leading cause of cancer deaths in women worldwide. Circular RNA circ_SETD2 (circ_SETD2), also termed as hsa_circ_0065173, is reported to be abnormally expressed in BC. Nevertheless, the role and mechanism of circ_SETD2 in BC are unclear. Expression of circ_SETD2, miR-155-5p, and SCUBE2 mRNA was evaluated by quantitative real-time polymerase chain reaction. Cell cycle progression, proliferation, apoptosis, migration, and invasion were determined by flow cytometry, MTT, and transwell assays. The relationship between circ_SETD2 or SCUBE2 and miR-155-5p was verified through a dual-luciferase reporter assay. The role of circ_SETD2 in BC in vivo was confirmed by a xenograft assay. circ_SETD2 and SCUBE2 were downregulated, while miR-155-5p was upregulated in BC tissues and cells. Both circ_SETD2 and SCUBE2 elevation arrested cell cycle progression, inhibited cell proliferation, migration, and invasion, and accelerated cell apoptosis in BC cells. Moreover, circ_SETD2 upregulation repressed BC growth in vivo. Importantly, circ_SETD2 modulated SCUBE2 expression through competitively binding to miR-155-5p in BC cells. Also, the inhibitory impacts of circ_SETD2 enhancement on the malignant behavior of BC cells were restored by miR-155-5p overexpression. Besides, SCUBE2 silencing abolished miR-155-5p downregulation mediated effects on the malignant behavior of BC cells. Therefore, circ_SETD2 curbed BC progression via upregulating SCUBE2 via binding to miR-155-5p.
Highlights
Breast cancer (BC) is the leading cause of cancer deaths in women worldwide
In view of the reduced expression of circ_SETD2 in BC tissues and cells, we further explored the role of circ_SETD2 in BC progression via a gain-of-function experiment. qRT-PCR exhibited that circ_SETD2 expression was enhanced in MCF-7 and MDA-MB-231 cells transfected with circ_SETD2 compared to the control group (Figure 2a)
The Propidium iodide (PI) cytometry assay for cell cycle revealed that circ_SETD2 enhancement boosted the number of MCF-7 and MDA-MB-231 cells in the G0/G1 stage of the cell cycle (Figure 2b and c)
Summary
Abstract: Breast cancer (BC) is the leading cause of cancer deaths in women worldwide. The relationship between circ_SETD2 or SCUBE2 and miR-155-5p was verified through a dualluciferase reporter assay. Circ_SETD2 and SCUBE2 were downregulated, while miR-155-5p was upregulated in BC tissues and cells. The role of circ_SETD2 in BC in vivo was confirmed by a xenograft assay. Both circ_SETD2 and SCUBE2 elevation arrested cell cycle progression, inhibited cell proliferation, migration, and invasion, and accelerated cell apoptosis in BC cells. Circ_SETD2 modulated SCUBE2 expression through competitively binding to miR-155-5p in BC cells. The inhibitory impacts of circ_SETD2 enhancement on the malignant behavior of BC cells were restored by miR-155-5p overexpression. Circ_SETD2 curbed BC progression via upregulating SCUBE2 via binding to miR-155-5p
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