RRC ID 54091
Author Yamada D, Fujikawa K, Kawabe K, Furuta T, Nakada M, Takarada T.
Title RUNX2 Promotes Malignant Progression in Glioma.
Journal Neurochem Res
Abstract Glioblastoma (GBM) is the most aggressive and lethal form of brain tumor. However, therapeutic strategies against malignant gliomas have not been completely established. Runt-related transcription factor 2 (Runx2) is an essential gene for skeletal development but its regulatory role in the malignant progression of glioma remains unclear. Here we investigated expression levels of RUNX2 in glioma tissues and its regulatory effects on aberrant growth of glioma cells. RUNX2 mRNA levels were higher in GBM tissues than that of normal brains or low-grade gliomas. RUNX2 protein was detected in five out of seven human GBM cell lines and its level was positively correlated with proliferative capacity. Stable transduction of dominant-negative Runx2 in rat-derived C6 glioma cells not only inhibited the promoter activity containing Runx2 response element, but also decreased mRNA expression levels of Runx2 target genes, such as Mmp13 and Spp1, as well as the proliferative capacity. Furthermore, transient introduction of Runx2-targeted siRNAs into C6 glioma cells significantly decreased mRNA expression levels of Mmp13 and Spp1 and the proliferative capacity. Furthermore, Runx2 knockdown suppressed both Ccnd1 mRNA expression and activation of the Ccnd1 promoter by forskolin, a PKA-activating reagent, in C6 glioma cells. Our results demonstrate that cross-talk between cAMP/PKA signaling and RUNX2 promotes a malignant phenotype of glioma cells.
Volume 43(11)
Pages 2047-2054
Published 2018-11-1
DOI 10.1007/s11064-018-2626-4
PII 10.1007/s11064-018-2626-4
PMID 30203400
MeSH Animals Brain Neoplasms / metabolism* Brain Neoplasms / pathology Cell Line, Tumor Cell Proliferation / genetics Core Binding Factor Alpha 1 Subunit / genetics Core Binding Factor Alpha 1 Subunit / metabolism* Gene Expression Regulation, Neoplastic / genetics* Glioma / genetics Glioma / metabolism* Humans Rats
IF 3.038
Times Cited 5
Human and Animal Cells C6(RCB2854)