Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University and Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University, Hangzhou 310016, Zhejiang Province, China.
Department of Orthopaedic Surgery, Ningbo First Hospital, Ningbo 315010, China.
Aging (Albany NY). 2023 Mar 9;15(5):1564-1590. doi: 10.18632/aging.204567.
Circular RNAs (circRNAs) have been demonstrated to have critical regulatory roles in tumorigenesis. However, the contribution of circRNAs to OS (osteosarcoma) remains largely unknown. circRNA deep sequencing was performed to the expression of circRNAs between OS and chondroma tissues. The regulatory and functional role of circRBMS3 (a circRNA derived from exons 7 to 10 of the gene, hsa_circ_0064644) upregulation was examined in OS and was validated and , upstream regulator and downstream target of circRBMS3 were both explored. RNA pull down, a luciferase reporter assay, biotin-coupled microRNA capture and fluorescence hybridization were used to evaluate the interaction between circRBMS3 and micro (mi)-R-424-5p. For tumorigenesis experiments, Subcutaneous and Orthotopic xenograft OS mouse models were built. Expression of circRBMS3 was higher in OS tissues due to the regulation of adenosine deaminase 1-acting on RNA (ADAR1), an abundant RNA editing enzyme. Our data indicated that ShcircRBMS3 inhibits the proliferation and migration of osteosarcoma cells. Mechanistically, we showed that circRBMS3 could regulate and , through 'sponging' miR-424-5p. Furthermore, knockdown of circRBMS3 inhibited malignant phenotypes and bone destruction of OS . Our results reveal an important role for a novel circRBMS3 in the growth and metastasis of malignant tumor cells and offer a fresh perspective on circRNAs in OS progression.
环状 RNA（circRNAs）已被证明在肿瘤发生中具有关键的调节作用。然而，circRNAs 对骨肉瘤（OS）的贡献在很大程度上仍然未知。进行了环状 RNA 深度测序，以比较 OS 和软骨瘤组织之间 circRNAs 的表达。在 OS 中检查了 circRBMS3（一种来自 基因外显子 7 到 10 的 circRNA，hsa_circ_0064644）上调的调节和功能作用，并验证了其上游调节剂和下游靶标。使用 RNA 下拉、荧光素酶报告基因测定、生物素偶联 microRNA 捕获和荧光杂交来评估 circRBMS3 与 micro（mi）-R-424-5p 之间的相互作用。为了进行肿瘤发生实验，构建了皮下和原位 OS 小鼠移植瘤模型。由于腺苷脱氨酶 1 作用于 RNA（ADAR1）的调节，丰富的 RNA 编辑酶，OS 组织中的 circRBMS3 表达上调。我们的数据表明，ShcircRBMS3 抑制骨肉瘤细胞的增殖和迁移。从机制上讲，我们表明 circRBMS3 可以通过“海绵”miR-424-5p 来调节 和 。此外，circRBMS3 的敲低抑制了 OS 的恶性表型和骨破坏。我们的结果揭示了一种新型 circRBMS3 在恶性肿瘤细胞生长和转移中的重要作用，并为 circRNAs 在 OS 进展中的作用提供了新的视角。
