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Transforming Growth Factor-β1-mediated Regulation of circ_DISP3 and ATF3 in Human Triple-negative Breast Cancer Cells
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Transforming Growth Factor-β1-mediated Regulation of circ_DISP3 and ATF3 in Human Triple-negative Breast Cancer Cells
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Transforming Growth Factor-β1-mediated Regulation of circ_DISP3 and ATF3 in Human Triple-negative Breast Cancer Cells
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Journal Article
Transforming Growth Factor-β1-mediated Regulation of circ_DISP3 and ATF3 in Human Triple-negative Breast Cancer Cells
2023
Overview
Background and objectivesWe previously reported that transforming growth factor-beta 1 (TGF-β1) promoted breast cancer progression and metastasis through inhibiting the expression of miR-4638-3p via directly targeting activating transcription factor 3 (ATF3). The present study aimed to elucidate the mechanisms of TGF-β1 downregulating ATF3 targeting miR-4638-3p via circRNA in MDA-MB231 cells.MethodsThree triple-negative human breast cancer cells (MDA-MB231, MDA-MB468, and MDA-MB453) were employed. In-silico analyses were used to identify the list of circRNAs targeting miR-4638-3p. RT-qPCR was performed to determine the expression of shortlisted circRNAs. Transient transfection and western blot analyses were carried out to identify the functional role of circ_DISP3. A dual-luciferase reporter assay was used to identify the direct binding of circ_DISP3 and miR-4638-3p.ResultsThere was an inverse correlation between the expression of circ_DISP3 and miR-4638-3p in these cells. Antisense oligos-mediated silencing of circ_DISP3 restored the function of miR-4638-3p, and downregulated ATF3 in MDA-MB231 cells. The luciferase reporter assay identified the direct binding of circ_DISP3 to miR-4638-3p in these cells.ConclusionsTGF-β1 influences the expression of ATF3 to stimulate circ_DISP3 to sponge miR-4638-3p in hBC cells. Hence, we suggest that the circ_DISP3/miR-4638-3p/ATF3 axis regulated by TGF-β1 may have potential applications for bone-metastatic breast cancer.
