Department of Orthopedic Surgery, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, 200072, PR China; Institute of Bone Tumor Affiliated to Tongji University, School of Medicine, Shanghai, 200072, PR China.
Department of Orthopedic Surgery, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, 200072, PR China; Institute of Bone Tumor Affiliated to Tongji University, School of Medicine, Shanghai, 200072, PR China.
Exp Cell Res. 2022 Mar 15;412(2):113050. doi: 10.1016/j.yexcr.2022.113050. Epub 2022 Jan 31.
Accumulating evidence has shown that many long non-coding RNAs (lncRNA) participate in the tumorigenesis, including osteosarcoma (OS). Of them, lncRNA ODRUL was previously reported to act as a possible oncogene in OS doxorubicin resistance. However, the underlying molecular mechanism of ODRUL involved in the progression of OS still remains to be thoroughly investigated. In the current study, we reported another mechanism by which ODRUL regulates OS progression. QRT-PCR and WB were conducted to detect ODRUL, miR-6874-3p and IL-6 expression in OS tissues and cells. The Kaplan-Meier was used to assess the relevance between the expression level of miR-6874-3p and the overall survival of OS patients. Wound healing assays and Transwell assays were used to evaluate the invasion and migration of OS cells. Furthermore, the binding sites of ODRUL and IL-6 to miR-6874-3p were predicted by bioinformatics and verified by dual-luciferase reporter gene assays. ODRUL and IL-6 were highly expressed in OS cells and tissues, while miR-6874-3p was expressed at low levels. The overall survival of high miR-6874-3p expression of OS patients was longer than that of low miR-6874-3p expression of OS patients. MiR-6874-3p overexpression markedly inhibited the progression of OS cells. Both ODRUL and IL-6 could bind to miR-6874-3p at the predicted binding sites which were authenticated by dual-luciferase reporter gene assay. MiR-6874-3p could inhibit OS cell proliferation and metastasis and ODRUL could reverse the suppression induced by miR-6874-3p in vivo. In conclusion, ODRUL could effectively sponge miR-6874-3p to upregulate the expression of IL-6 in OS progression.
越来越多的证据表明，许多长非编码 RNA（lncRNA）参与肿瘤的发生，包括骨肉瘤（OS）。其中，lncRNA ODRUL 先前被报道在 OS 多柔比星耐药中作为一种可能的癌基因。然而，ODRUL 参与 OS 进展的潜在分子机制仍有待深入研究。在本研究中，我们报道了 ODRUL 调节 OS 进展的另一种机制。通过 QRT-PCR 和 WB 检测 OS 组织和细胞中 ODRUL、miR-6874-3p 和 IL-6 的表达。Kaplan-Meier 用于评估 miR-6874-3p 的表达水平与 OS 患者总生存期之间的相关性。伤口愈合实验和 Transwell 实验用于评估 OS 细胞的侵袭和迁移。此外，通过生物信息学预测 ODRUL 和 IL-6 与 miR-6874-3p 的结合位点，并通过双荧光素酶报告基因实验验证。ODRUL 和 IL-6 在 OS 细胞和组织中高表达，而 miR-6874-3p 表达水平较低。高 miR-6874-3p 表达的 OS 患者的总生存期长于低 miR-6874-3p 表达的 OS 患者。miR-6874-3p 过表达显著抑制 OS 细胞的进展。ODRUL 和 IL-6 均可与预测的结合位点结合miR-6874-3p 通过双荧光素酶报告基因实验证实。miR-6874-3p 可抑制 OS 细胞增殖和转移，ODRUL 可逆转 miR-6874-3p 在体内的抑制作用。总之，ODRUL 可有效吸附 miR-6874-3p，上调 OS 进展中 IL-6 的表达。
