Thus, we propose that Wnt3a belongs to the arsenal of factors capable of stimulating the induction of M2-like phenotype on microglial cells, which contributes to the poor prognostic of glioblastoma, reinforcing that Wnt/β-catenin pathway can be a potential therapeutic target to attenuate glioblastoma progression.
SIGNIFICANCE: These findings identify the β-catenin-USP1-EZH2 signaling axis as a critical mechanism for glioma tumorigenesis that may serve as a new therapeutic target in glioblastoma.
In terms of mechanism, we found that SNHG7 directly inhibited miR-5095, which targeted the 3' UTR of CTNNB1 mRNA and subsequently downregulated the Wnt/β-catenin signaling pathway in GBM.
Additionally, tunicamycin increased the expression of maternally expressed gene-3 (MEG-3) and wingless/integrated (Wnt)/β-catenin in glioblastoma cells.
In conclusion, miR-370 inhibited the proliferation of human glioma cells by regulating the levels of β-catenin and the activation of FOXO3a, suggesting that miR-370 was a tumor suppressor in the progression of human astrocytoma and glioblastoma cells.
Tumor growth rate and final tumor weight were significantly increased in the animals with the glioblastoma derived from transfected U87-H4645 cells, compared to untransfected and vector control (p<0.01). mRNA expression of β-catenin, CD44, ICAM-1, and MMP-2 in the glioblastoma derived from the transfected U87-H4645 tumors was significantly increased compared with tumors derived from untransfected and vector-control U87 cells (p<0.01).
<i>NEAT1</i> depletion also inhibited GBM cell growth and invasion in the intracranial animal model.<b>Conclusions:</b> The EGFR/<i>NEAT1</i>/EZH2/β-catenin axis serves as a critical effector of tumorigenesis and progression, suggesting new therapeutic directions in glioblastoma.<i></i>.
Subsequent genetic inhibition experiments showed that suppression of MACF1 selectively inhibited glioblastoma cell proliferation and migration in cell lines established from patient derived xenograft mouse models and immortalized glioblastoma cell lines that were associated with downregulation of the Wnt-signaling mediators, Axin1 and β-catenin.
Methylation-mediated silencing of microRNA-211 promotes cell growth and epithelial to mesenchymal transition through activation of the AKT/β-catenin pathway in GBM.
Here, we identified that β-catenin mRNA and protein levels were up-regulated in GBM tissues and four kinds of glioblastoma cell lines, including T98G, A172, U87, and U251 cells, compared with normal brain tissue and astrocytes.
Inhibition of Bevacizumab-induced Epithelial-Mesenchymal Transition by BATF2 Overexpression Involves the Suppression of Wnt/β-Catenin Signaling in Glioblastoma Cells.
Western blot analysis confirmed decreased expression of the Wnt signaling pathway genes Axin2, c-myc, and cyclin D1 in miR-577 transfected cells. miR-577 expression is down-regulated in glioblastoma. miR-577 directly targets Wnt signaling pathway components LRP6 and β-catenin. miR-577 suppresses glioblastoma multiforme (GBM) growth by regulating the Wnt signaling pathway.
The depletion of β-catenin potentiated PI3K/mTOR inhibitor-induced cytotoxicity and the inhibition of MSK1 synergized with PI3K/mTOR inhibitors to extend survival in an intracranial animal model and decreased phosphorylation of β-catenin at Ser(552) These observations suggest that MSK1/β-catenin signaling serves as an escape survival signal upon PI3K/mTOR inhibition and provides a strong rationale for the combined use of PI3K/mTOR and MSK1/β-catenin inhibition to induce lethal growth inhibition in human GBM.
Recent reports describe BRAF<sup>V600E</sup> mutation in malignant peripheral nerve sheath tumors, and aberrant Wnt signaling and CTNNB1 (β-catenin gene) mutations have been described in GBM.
In 74 gliomas of different histological grade and in 24 glioblastoma cell lines, protein expression of WNT member 3a (WNT3a), β-catenin and transcription factor 4 (TCF4) was investigated by immunohistochemistry, western blotting, immunofluorescence and immunocytochemistry.
Our results revealed that β-catenin and miR-21 were concordantly expressed in GBM cell lines, and SFN significantly reduced miR-21 expression through inhibiting the Wnt/β-catenin/TCF4 pathway.
Therefore, it was hypothesized that low‑density lipoprotein receptor‑related protein 6 (LRP6) may be involved in activating the Wnt/β‑catenin pathway in the progression of GBM.