Introduction

Clinical specimens used for the expression analysis of miRNA were as follows: 9 anaplastic oligodendrogliomas, 10 meningiomas, and 8 normal brain tissues. Additionally, glioma cell lines, J3T-1 and J3T-2 were used for the gene expression analysis and in vitro experiments.

Methods

Clinical specimens used for the expression analysis of miRNA were follow: 9 anaplastic oligodendrogliomas, 10 meningiomas, 8 normal brain tissues. Additionally, glioma cell lines, J3T-1, and J3T-2 were used for the gene expression analysis and in vitro experiments.

Results

The expression level of miR-190a was significantly downregulated in glioma tissues, meningioma tissues, and cell lines compared with normal brain tissues. Extrinsic miR-190a decreased the number of viable glioma cells. The expression of NRG3 and p-Akt, (which is a putative downstream target of NRG3) were decreased by the transfection with miR-190a. Also, silencing of NRG3 exhibited similar effects to extrinsic miR-190a. Luciferase activity assay revealed that NRG3 is a direct target of miR-190a. NRG3 has been shown to be a ligand of ERBB4. In fact, treatment with Afatinib, a pan-HER family inhibitor, significantly suppressed the growth of glioma cells when compared to treatment with Gefitinib, an EGFR inhibitor, or Lapatinib, an EGFR and ERBB2 inhibitor. Concurrently, Afatinib successfully decreased the level of p-Akt in glioma cells.

Conclusion

miR-190a functions as a tumor-suppressor in canine glioma by targeting NRG3, and the NRG3/ERBB4 cascade might be a promising therapeutic target of canine glioma.

Funding Information

No funding was used for this project.