Osteosarcoma Cell-Derived Exosomal miR-1307 Promotes Tumorgenesis via Targeting AGAP1

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.

Automated summary

The study demonstrates that OS cell-derived exosomal miR-1307 promotes the proliferation, migration, and invasion of OS cells by targeting AGAP1. The miR-1307-AGAP1 axis may play a significant role in the future treatment of OS.