In the current study, we determined whether myeloid ecotropic insertion site 1 (Meis1) is involved in the development of malignant brain tumors by performing intracranial transplantation of mouse NE4C neuronal progenitor cell lines overexpressing Meis1. Then, we conducted immunostaining to compare the tumors with the control NE4C cells. According to our results, multiple characteristics of the malignant progression were observed in the tumors. Consistent with these results, the survival rate of the mice transplanted with Meis1-overexpressing cells was significantly reduced compared with the control mice. We then sought to identify genes involved in the malignant progression caused by Meis1 overexpression, and we performed RNA sequencing on the tumors. Among the genes identified, we focused on DNA methyltransferase B (Dnmt3b), and transfected short hairpin RNA (shRNA) against Dnmt3b into NE4C cells overexpressing Meis1. To examine the possible effects of Meis1 and Dnmt3b on the malignant progression, we intracranially transplanted these transfectants, and checked the pathological features of the brain tumors, as well as the survival rate of the transplanted mice. The results showed that Dnmt3b expression was upregulated by Meis1 and that Wnt7a, which is related to neuronal differentiation and Notch signaling correlated with suppressive functions in brain tumors, was downregulated, leading to tumor malignancy.