Zhu Xiufang, Li Lei
Department of Medical Imaging, The First People's Hospital of Lianyungang, Lianyungang, Jiangsu 222002, China.
J Oncol. 2021 Nov 22;2021:8461740. doi: 10.1155/2021/8461740. eCollection 2021.
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.
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.
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/-catenin pathway in BC cells via SOX4.
Our study concluded that circ-DONSON knockdown hindered cell proliferation and radioresistance through the SOX4/Wnt/-catenin pathway in BC.
环状RNA已被证实是乳腺癌(BC)发展过程中的关键调节因子。Circ-DONSON参与了胶质瘤和胃癌的进展。然而,circ-DONSON在BC中的生物学作用仍不清楚,本研究旨在探讨circ-DONSON在BC中的生物学作用。
本研究收集了人体组织样本和BC细胞系。针对circ-DONSON的小干扰RNA(siRNA)被转染到BC细胞系中以沉默circ-DONSON。采用定量实时聚合酶链反应检测circ-DONSON的表达。使用细胞计数试剂盒-8(CCK-8)、5-溴-2'-脱氧尿苷酶联免疫吸附测定(BrdU-ELISA)、集落形成和半胱天冬酶-3活性测定来评估细胞增殖、细胞存活和细胞活力。采用蛋白质免疫印迹分析检测蛋白质表达水平。
我们的研究结果表明,circ-DONSON在BC组织和细胞系中高表达。CCK-8和BrdU-ELISA测定表明,circ-DONSON敲低抑制了BC细胞增殖。此外,细胞存活、细胞活力和半胱天冬酶-3活性测定表明,circ-DONSON敲低降低了BC细胞的放射抗性。机制上,circ-DONSON通过SRY盒转录因子4(SOX4)调节BC细胞增殖和放射抗性。SOX4过表达显著挽救了circ-DONSON敲低对BC细胞增殖和放射抗性的影响。此外,circ-DONSON通过SOX4激活了BC细胞中的Wnt/β-连环蛋白信号通路。
我们的研究得出结论,circ-DONSON敲低通过BC中的SOX4/Wnt/β-连环蛋白信号通路阻碍细胞增殖和放射抗性。