Open Access
ARTICLE
miR-148-3p Inhibits Growth of Glioblastoma Targeting DNA Methyltransferase-1 (DNMT1)
Yongtao Li*, Fanyu Chen*, Jiancheng Chu*, Chao Wu*, Yuan Li†, Heng Li†, Hongxin Ma*
* Department of Neurosurgery, Tengzhou Central People’s Hospital, Tengzhou, Shandong, P.R. China
† School of Medicine, Shandong University, Jinan, Shandong, P.R. China
Oncology Research 2019, 27(8), 911-921. https://doi.org/10.3727/096504019X15516966905337
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 that the expression of miR-148-3p in glioma
tissues was decreased compared with adjacent nontumor 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 downregulated and accompanied with upregulation of DNMT1 and
hypermethylation level of RUNX3 promoter region. miR-148-3p overexpression 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 upregulating RUNX3
expression. Mechanistically, the 3 -untranslated region (3 -UTR) of DNMT1 was a direct target of miR-148-3p.
Overexpression 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.
Keywords
Cite This Article
Li, Y., Chen, F., Chu, J., Wu, C., Li, Y. et al. (2019). miR-148-3p Inhibits Growth of Glioblastoma Targeting DNA Methyltransferase-1 (DNMT1).
Oncology Research, 27(8), 911–921.