Effect of Ras-guanine nucleotide release factor 1-mediated H-Ras/ERK signaling pathway on glioma

Objective: To investigate the function of Ras-guanine nucleotide release factor 1 (Ras-GRF1) in glioma through mediating H-Ras/ERK signaling pathway. Methods: Ras-GRF1, H-Ras, K-Ras and N-Ras expressions in glioma and normal brain tissues were detected via Immunohistochemistry. Glioma cells (U87 cells, U251 cells and primary human glioma cells) were transfected with Ras-GRF1 siRNA, H-Ras siRNA and/or Ras-GRF1 lentivirus activation particles. Then, the following aspects were evaluated: cell proliferation by MIT assay, clonogenic ability by the plate clone formation experiment, cell migration and invasion by Wound-healing and Transwell assays, and cell apoptosis by Annexin-V-FITC/PI staining. The protein expressions were measured by Western blotting. Subcutaneous and orthotopic mouse models of glioma were conducted to determine the role of Ras-GRF1 in glioma tumorigenesis. Results: Ras-GRF1, H-Ras, K-Ras and N-Ras expressions were upregulated in the glioma tissues, which were correlated with the WHO grade of glioma. Besides, Ras-GRF1 expression was positively related to H-Ras expression. Ras-GRF1 siRNA could reduce the expression of H-Ras and p-ERK/ERK in glioma cell. H-Ras siRNA inhibited the proliferation, clone formation, migration and invasion, and enhance the apoptosis of glioma cells, which, however, were reversed by Ras-GRF1 lentivirus activation particles. In vivo experiments also revealed that Ras-GRF1 shRNA reduced the volume and weight of the tumors in the nude mice, with down-regulations of H-Ras and p-ERK/ERK. Conclusion: Ras-GRF1 was upregulated in glioma tissues and correlated with its malignancy and prognosis. Silencing Ras-GRF1, through mediating H-Ras/ERK pathway, may suppress the growth and metastasis of glioma.

Automated summary

The study revealed that Ras-GRF1 was upregulated in glioma tissues and correlated with the malignancy and prognosis of the tumors. Silencing Ras-GRF1, through mediating the H-Ras/ERK pathway, could suppress the growth and metastasis of glioma.