Osteosarcoma Cell-Derived Exosomal miR-1307 Promotes Tumorgenesis via Targeting AGAP1.
Osteosarcoma Cell-Derived Exosomal miR-1307 Promotes Tumorgenesis via Targeting AGAP1.
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骨肉瘤细胞来源的外泌体 miR-1307 通过靶向 AGAP1 促进肿瘤发生
DOI：
10.1155/2021/7358153
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发表时间：
2021
影响因子：
--
通讯作者：
Wang W
中科院分区：
文献类型：
--
作者：
Han F;Pu P;Wang C;Ding X;Zhu Z;Xiang W;Wang W
骨肉瘤(OS)的发生与多种microRNAs(MiRNAs)的异常表达有关。胞外体miRNAs在细胞内通讯中受到越来越多的关注。MIR-1307在许多癌症中的作用已经被研究过，但它在OS中的作用还没有研究过。我们假设OS来源的外体miR-1307调控OS肿瘤的发生。首先，我们发现OS细胞衍生的外切体(Exos)显著促进OS细胞的增殖、迁移和侵袭。其次，我们发现miR-1307在OS细胞衍生的外切体(OS-Exos)、人OS组织和OS细胞系中都有高表达。将miR-1307抑制剂导入OS细胞后，提取OS-Exos，使OS-Exos中miR-1307的表达水平显著降低。当OS-Exos中miR-1307水平显著降低时，OS-Exos对OS细胞迁移、侵袭和增殖的作用也明显减弱。进一步利用TargetScan、miRDB和mirDIP数据库，我们确定AGAP1是miR-1307的靶基因。MiR-1307过表达可抑制AGAP1基因的表达。我们还发现AGAP1在人OS组织和OS细胞系中的表达水平较低。荧光素酶基因分析表明，miR-1307与AGAP1的3‘端非编码区直接结合。临床研究中MIR-1307与AGAP1呈负相关。MIR-1307可显著促进OS细胞的增殖、迁移和侵袭。此外，AGAP1的上调可显著抑制miR-1307在OS中的作用。综上所述，我们的研究表明，OS细胞来源的外体miR-1307通过靶向AGAP1促进OS细胞的增殖、迁移和侵袭，miR-1307-AGAP1轴可能在未来OS的治疗中发挥重要作用。
The occurrence of osteosarcoma (OS) is associated with abnormal expression of many microRNAs (miRNAs). Exosomal miRNAs get much more attentions in intracellular communications. miR-1307 has been studied in many cancers, but its effects in OS have not been studied. We hypothesized that OS-derived exosomal miR-1307 regulates OS tumorigenesis. First, we found OS cell-derived exosomes (Exos) significantly promoted the proliferation, migration, and invasion of OS cells. Secondly, we found miR-1307 was highly expressed in OS cell-derived exosomes (OS-Exos), human OS tissues, and OS cell lines. Then, OS-Exos were extracted after OS cells were cultured and transfected with miR-1307 inhibitor, and the level of miR-1307 in OS-Exos was significantly reduced. When the level of miR-1307 in OS-Exos was significantly reduced, the effects of OS-Exos on migration, invasion, and proliferation of OS cells were also significantly weakened. Furthermore, using TargetScan, miRDB, and mirDIP databases, we identified that AGAP1 was a target gene of miR-1307. Overexpression of miR-1307 could inhibit the expression of AGAP1 gene. We also found AGAP1 was lower expressed in human OS tissues and OS cell lines. Luciferase gene indicated that miR-1307 directly bound the 3'-UTR of AGAP1. miR-1307 was negatively correlated with AGAP1 in clinical study. miR-1307 could significantly promote the proliferation, migration, and invasion of OS cells. In addition, upregulation of AGAP1 could significantly inhibit the role of miR-1307 in OS. In conclusion, our study suggests that OS cell-derived exosomal miR-1307 promotes the proliferation, migration, and invasion of OS cells via targeting AGAP1, and miR-1307-AGAP1 axis may play an important role in the future treatment of OS.
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