Back to Search
Start Over
Epigenetic Regulation of the miR142-3p/Interleukin-6 Circuit in Glioblastoma.
- Source :
-
Molecular Cell . Dec2013, Vol. 52 Issue 5, p693-706. 14p. - Publication Year :
- 2013
-
Abstract
- Summary: Epigenetic regulation plays a critical role in glioblastoma (GBM) tumorigenesis. However, how microRNAs (miRNAs) and cytokines cooperate to regulate GBM tumor progression is still unclear. Here, we show that interleukin-6 (IL-6) inhibits miR142-3p expression and promotes GBM propagation by inducing DNA methyltransferase 1-mediated hypermethylation of the miR142-3p promoter. Interestingly, miR142-3p also suppresses IL-6 secretion by targeting the 3′ UTR of IL-6. In addition, miR142-3p also targets the 3′ UTR and suppresses the expression of high-mobility group AT-hook 2 (HMGA2), leading to inhibition of Sox2-related stemness. We further show that HMGA2 enhances Sox2 expression by directly binding to the Sox2 promoter. Clinically, GBM patients whose tumors present upregulated IL-6, HMGA2, and Sox2 protein expressions and hypermethylated miR142-3p promoter also demonstrate poor survival outcome. Orthotopic delivery of miR142-3p blocks IL-6/HMGA2/Sox2 expression and suppresses stem-like properties in GBM-xenotransplanted mice. Collectively, we discovered an IL-6/miR142-3p feedback-loop-dependent regulation of GBM malignancy that could be a potential therapeutic target. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 10972765
- Volume :
- 52
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Molecular Cell
- Publication Type :
- Academic Journal
- Accession number :
- 92900634
- Full Text :
- https://doi.org/10.1016/j.molcel.2013.11.009