Abstract
Background Circular RNAs have been validated as critical regulators in the development of breast cancer (BC). Circ-DONSON is involved in the progression of glioma and gastric cancer. However, the biological role of circ-DONSON in BC remains unclear, and the aim of this study was to explore the biological role of circ-DONSON in BC. Methods Human tissue samples and BC cell lines were collected in this study. siRNAs against circ-DONSON were transfected into BC cell lines for silencing of circ-DONSON. Quantitative real-time PCR was used to test the circ-DONSON expression. Cell counting kit-8 (CCK-8), 5-bromo-2′ deoxyuridine enzyme-linked immunosorbent assay (BrdU-ELISA), colony formation, and caspase-3 activity assays were used to assess cell proliferation, cell survival, and cell viability. Western blotting analysis was used to detect the protein expression levels. Results Our findings showed that circ-DONSON showed high expression in BC tissues and cell lines. CCK-8 and BrdU-ELISA assays showed that circ-DONSON knockdown inhibited BC cell proliferation. Moreover, cell survival, cell viability, and caspase-3 activity assays showed that circ-DONSON knockdown reduced the radioresistance of BC cells. Mechanistically, circ-DONSON regulated BC cell proliferation and radioresistance via SRY-box transcription factor 4 (SOX4). SOX4 overexpression significantly rescued the effect of circ-DONSON knockdown on BC cell proliferation and radioresistance. Moreover, circ-DONSON activated the Wnt/β-catenin pathway in BC cells via SOX4. Conclusion Our study concluded that circ-DONSON knockdown hindered cell proliferation and radioresistance through the SOX4/Wnt/β-catenin pathway in BC.
Highlights
Breast cancer (BC) is one of the most common cancers in women worldwide [1, 2]
Radiotherapy is a main treatment for breast cancer (BC) patients, radioresistance leads to limited therapeutic efficacy [3, 4]. erefore, it is urgently required to explore the molecular mechanisms of BC progression and radioresistance
Circ-DONSON Was Highly Expressed in BC Tissues and Cell Lines
Summary
Breast cancer (BC) is one of the most common cancers in women worldwide [1, 2]. radiotherapy is a main treatment for BC patients, radioresistance leads to limited therapeutic efficacy [3, 4]. erefore, it is urgently required to explore the molecular mechanisms of BC progression and radioresistance.As a recently discovered member of the noncoding RNA family, circular RNAs (circRNAs) are characterized by a covalently closed continuous loop structure [5]. Hsa_circRNA_103809 regulates the colorectal cancer cell proliferation and migration via the miR-532-3p/FOXO4 axis [9]. Our findings showed that circ-DONSON showed high expression in BC tissues and cell lines. CCK-8 and BrdU-ELISA assays showed that circ-DONSON knockdown inhibited BC cell proliferation. Cell survival, cell viability, and caspase-3 activity assays showed that circ-DONSON knockdown reduced the radioresistance of BC cells. Circ-DONSON regulated BC cell proliferation and radioresistance via SRY-box transcription factor 4 (SOX4). SOX4 overexpression significantly rescued the effect of circ-DONSON knockdown on BC cell proliferation and radioresistance. Circ-DONSON activated the Wnt/ β-catenin pathway in BC cells via SOX4. Our study concluded that circ-DONSON knockdown hindered cell proliferation and radioresistance through the SOX4/Wnt/β-catenin pathway in BC
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