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MiR-148-3p inhibits growth of glioblastoma targeting DNA methyltransferase-1 (DNMT1).

Yongtao Li,Fanyu Chen,Jiancheng Chu,Chao Wu,Yuan Li,Heng Li

Published 2019 in Oncology Research

ABSTRACT

To date, miR-148-3p and DNMT1-recombinant human runt-related transcription factor 3 (RUNX3) axis have been linked to cell proliferation, migration and invasion; however, their roles and relationships in human glioblastoma multiforme (GBM) are still not clear. Here, we found the expression of miR-148-3p in gliomas tissues was decreased compared with adjacent non-tumor tissues, and correlated with WHO grade, tumor size and prognosis as well as DNMT1 and RUNX3 expressions. Compared with NHA cells, the expression of miR-148-3p in U87 and U251 cells was also down-regulated, and accompanied with up-regulation of DNMT1 and hyper-methylation level of RUNX3 promoter region. MiR-148-3p over-expression induced apoptosis and cell cycle arrest of U87 and U251 cells, and affected cell migration and invasion. MiR-148-3p mimics effectively suppressed the expression of DNMT1 and methylation of RUNX3 promoter, finally up-regulating RUNX3 expression. Mechanistically, the 3'-untranslated region (3'-UTR) of DNMT1 was a direct target of miR-148-3p. Over-expression of miR-148-3p or inhibition of DNMT1 induced the expression of E-cadherin, and reduced the expressions of N-cadherin, Vimentin, MMP-2 and MMP-9. In conclusion, miR-148-3p directly repressed the expression of DNMT1, and inhibited proliferation, migration and invasion by regulating DNMT1-RUNX3 axis and the epithelial-mesenchymal transition in GBM. Our findings provide a new foundation for treatment of patients with GBM.

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