Department of Orthopaedics, The First Affiliated Hospital of the Medical College, Shihezi University, Shihezi, China.
Medical College, Shihezi University, Shihezi, China.
Biomed Res Int. 2021 Mar 25;2021:7358153. doi: 10.1155/2021/7358153. eCollection 2021.
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.
骨肉瘤（OS）的发生与许多 microRNAs（miRNAs）的异常表达有关。细胞内通讯中，外泌体 miRNAs 受到了更多关注。miR-1307 在许多癌症中都有研究，但在 OS 中的作用尚未研究。我们假设 OS 来源的外泌体 miR-1307 调节 OS 肿瘤发生。首先，我们发现 OS 细胞来源的外泌体（Exos）显著促进了 OS 细胞的增殖、迁移和侵袭。其次，我们发现 miR-1307 在 OS 细胞来源的外泌体（OS-Exos）、人 OS 组织和 OS 细胞系中高表达。然后，在 OS 细胞培养并转染 miR-1307 抑制剂后提取 OS-Exos，OS-Exos 中的 miR-1307 水平显著降低。当 OS-Exos 中的 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显著减弱。此外，通过使用 TargetScan、miRDB 和 mirDIP 数据库，我们鉴定出 AGAP1 是 miR-1307 的靶基因。miR-1307 的过表达可以抑制 AGAP1 基因的表达。我们还发现 AGAP1 在人 OS 组织和 OS 细胞系中表达较低。荧光素酶基因表明 miR-1307 可直接结合 AGAP1 的 3'-UTR。临床研究表明 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，上调 AGAP1 可显著抑制 miR-1307 在 OS 中的作用。综上所述，本研究表明，OS 细胞来源的外泌体 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。
