a Department of Orthopedics, Huaihe Hospital of Henan University , Kaifeng , Henan , China.
b Department of Orthopedics, The Second People's Hospital of Nanyang City , Nanyang , Henan , China.
Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):3322-3328. doi: 10.1080/21691401.2019.1648285.
Long non-coding RNAs (LncRNAs) have been proven to be involved in the progression of osteosarcoma. LncRNA DLEU1 was found to act as an oncogene in various types of cancer. In this study, we aimed to explore the biological functions of DLEU1 in osteosarcoma and the specific mechanism. Our results showed that DLEU1 was highly expressed in osteosarcoma tissue specimens and cells. Downregulation of DLEU1 in osteosarcoma cells inhibited the cell proliferation, migration and invasion. Further mechanistic analysis and functional assays demonstrated that DLEU1 exerted its role by sponging microRNA (miR)-671-5p in osteosarcoma cells. Moreover, DEAD-box helicase 5 (DDX5) was confirmed as the target of miR-671-5p. Furthermore, rescue assays indicated that miR-671-5p inhibitor significantly reversed the effects of DLEU1 knockdown on osteosarcoma cell proliferation and invasion while restoration of DDX5 rescued the proliferation and invasion of osteosarcoma cells transfected with miR-671-5p mimics. In conclusion, DLEU1 acted as an oncogene in osteosarcoma by directly sponging miR-671-5p and regulating the expression of DDX5. These findings suggested that DLEU1 might be a novel therapeutic target in the treatment of osteosarcoma.
长链非编码 RNA(lncRNA)已被证明参与骨肉瘤的进展。LncRNA DLEU1 已被发现作为多种类型癌症的癌基因发挥作用。在这项研究中,我们旨在探讨 DLEU1 在骨肉瘤中的生物学功能及其具体机制。我们的研究结果表明,DLEU1 在骨肉瘤组织标本和细胞中高表达。下调骨肉瘤细胞中的 DLEU1 抑制了细胞增殖、迁移和侵袭。进一步的机制分析和功能测定表明,DLEU1 通过在骨肉瘤细胞中海绵吸附 microRNA(miR)-671-5p 发挥作用。此外,DEAD -box 解旋酶 5(DDX5)被证实为 miR-671-5p 的靶标。此外,挽救实验表明,miR-671-5p 抑制剂显著逆转了 DLEU1 敲低对骨肉瘤细胞增殖和侵袭的影响,而 miR-671-5p 模拟物转染的 DDX5 恢复则挽救了骨肉瘤细胞的增殖和侵袭。总之,DLEU1 通过直接海绵吸附 miR-671-5p 并调节 DDX5 的表达,在骨肉瘤中发挥癌基因作用。这些发现表明 DLEU1 可能成为骨肉瘤治疗的新靶点。