Long noncoding RNA DLEU1 aggravates osteosarcoma carcinogenesis via regulating the miR-671-5p/DDX5 axis
Long noncoding RNA DLEU1 aggravates osteosarcoma carcinogenesis via regulating the miR-671-5p/DDX5 axis
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DOI：
10.1080/21691401.2019.1648285
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发表时间：
2019-01-01
影响因子：
5.8
通讯作者：
Wang, Xiao
中科院分区：
文献类型：
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作者：
Chen, Xinxin;Zhang, Chengyong;Wang, Xiao
长链非编码rna （LncRNAs）已被证明参与骨肉瘤的进展。LncRNA DLEU1被发现在各种类型的癌症中作为致癌基因。在本研究中，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，在骨肉瘤组织标本和细胞中，DLEU1高度表达。在骨肉瘤细胞中下调DLEU1可抑制细胞的增殖、迁移和侵袭。进一步的机制分析和功能分析表明，dolu1通过在骨肉瘤细胞中海绵化microRNA (miR)-671-5p发挥其作用。此外，DEAD-box解旋酶5 （DDX5）被证实是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dlu1敲低对骨肉瘤细胞增殖和侵袭的影响，而恢复DDX5则挽救了转染miR-671-5p模拟物的骨肉瘤细胞的增殖和侵袭。综上所述，DLEU1通过直接海绵化miR-671-5p，调控DDX5的表达，在骨肉瘤中发挥致癌基因的作用。这些发现提示，DLEU1可能是治疗骨肉瘤的一个新的治疗靶点。
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.