Department of Orthopaedics, China-Japan Union Hospital of Jilin University , Changchun, Jilin, China.
Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University , Changchun, Jilin, China.
Cell Cycle. 2020 Sep;19(17):2139-2147. doi: 10.1080/15384101.2020.1792636. Epub 2020 Aug 11.
Traditionally, circular RAN hsa_circ_0008035 was proven to function as a tumor inhibitor in gastric cancer. Nevertheless, much less was known about hsa_circ_0008035 in osteosarcoma (OSA). This project was undertaken to assess the role of hsa_circ_0008035 in OSA. Hsa_circ_0008035 level in serum of OSA patients, OSA tissues and cell lines were measured by reverse transcription-quantitative PCR. After downregulation or overexpression of hsa_circ_0008035, cell proliferation, apoptosis and migration were tested in MG63, SAOS-2 or hFOB1.19 cells. Meanwhile, the expression level of miR-375 was analyzed. The binding between hsa_circ_0008035 and miR-375 was confirmed using bioinformatics and luciferase assay. Subsequently, the effects of miR-375 inhibition on MG63 cell growth and migratory potential were reevaluated. Eventually, the activating status of Notch pathway was assessed by Western blot. Our results demonstrated that hsa_circ_0008035 was overexpressed in serum of OSA patients, OSA tissues and cells. Silencing hsa_circRNA_0008035 impeded OSA cell growth and migration, while hsa_circ_0008035 facilitated cell behaviors of hFOB1.19 cells. Additionally, hsa_circ_0008035 negatively modulated miR-375 expression. Meanwhile, miR-375 inhibition overturned the suppressive effects of silencing hsa_circRNA_0008035 on OSA cell behaviors. Furthermore, silencing hsa_circ_0008035 perturbed Notch pathway by adjusting miR-375 expression. In conclusion, silencing hsa_circRNA_0008035 exerted repressive function on OSA cell growth and migration and Notch pathway by accelerating miR-375.
传统上，环状 RAN hsa_circ_0008035 被证明在胃癌中作为肿瘤抑制剂发挥作用。然而，关于 hsa_circ_0008035 在骨肉瘤（OSA）中的作用知之甚少。本项目旨在评估 hsa_circ_0008035 在 OSA 中的作用。通过逆转录定量 PCR 测量 OSA 患者、OSA 组织和细胞系中的 hsa_circ_0008035 水平。在 MG63、SAOS-2 或 hFOB1.19 细胞中下调或过表达 hsa_circ_0008035 后，检测细胞增殖、凋亡和迁移。同时，分析 miR-375 的表达水平。通过生物信息学和荧光素酶测定证实 hsa_circ_0008035 与 miR-375 之间的结合。随后，重新评估 miR-375 抑制对 MG63 细胞生长和迁移潜能的影响。最后，通过 Western blot 评估 Notch 通路的激活状态。我们的结果表明，hsa_circ_0008035 在 OSA 患者、OSA 组织和细胞的血清中过度表达。沉默 hsa_circRNA_0008035 抑制 OSA 细胞的生长和迁移，而 hsa_circ_0008035 促进 hFOB1.19 细胞的细胞行为。此外，hsa_circ_0008035 负调节 miR-375 的表达。同时，miR-375 抑制逆转了沉默 hsa_circRNA_0008035 对 OSA 细胞行为的抑制作用。此外，通过调节 miR-375 的表达，沉默 hsa_circ_0008035 扰乱了 Notch 通路。总之，通过加速 miR-375，沉默 hsa_circRNA_0008035 对 OSA 细胞的生长和迁移以及 Notch 通路发挥抑制作用。
