We used computational target gene prediction, <i>in vitro</i> cell culture, immunoblotting, quantitative real-time PCR, ATP measurements, luciferase reporter assays, wound-healing assays, Transwell assays, RNA immunoprecipitation PCR, co-immunoprecipitation, flow cytometry and tumor xenografts to study the regulation of the PKM2/β-catenin axis in glioma.
In conclusion, our study validates a pathogenetic role of miR-19 in glioma and establishes a potentially regulatory and signaling involving miR-19 /RUNX3/β-catenin, also suggesting miR-19 may be a candidate therapeutic target in glioma.
Treatment with demethylating agent (5-aza-2'-deoxycytidine) or exogenous expression of Six3 restored Six3 production and resulted in suppression of cell cycle G1/S transition, proliferation and invasion and down-regulation of the expression of Wnt1, p-GSK3-β, β-catenin and cyclin D1 in glioma U251 cells.
Accordingly, we aimed to investigate NCTD as an anti-neoplastic drug that inhibits the Wnt/β‑catenin pathway via promoter demethylation of Wnt inhibitory factor-1 (WIF-1) in glioma growth in vitro.
As we demonstrated earlier that α5β1 integrin may be considered as a therapeutic target in high grade glioma through its contribution to glioma cell migration and resistance to chemotherapy, we addressed here the potential relationship between α5β1 integrin and beta-catenin activation in glioma cells.
Expression of WNT3a, cytoplasmic β-catenin and TCF4 was significantly associated with the histological malignancy grade and with a worse prognosis for patients with glioma.
Down-regulation of USP9X also consistently inhibits the tumorigenicity of primary glioma cells in vivo.In summary, these results indicate that USP9X stabilizes β-catenin and activates Wnt/β-catenin signal pathway to promote glioma cell proliferation and survival.
Taken together, these data suggest that KLF8 modulates glioma cell resistance to TMZ via activation of β-catenin; therefore, therapies that inhibit KLF8 levels in glioma can enhance the efficacy of TMZ treatment.
In conclusion, our study suggests that SPOCK1 promotes proliferation, migration and invasion in glioma cells by activating PI3K/AKT and Wnt/β-catenin pathways, which provides a potential theoretical basis for clinical treatment of glioma.
Here we studied phosphoY142 (PY142) β-catenin and dephospho S/T β-catenin (a classical Wnt transducer) in glioma biopsies, GBM cell lines and biopsy-derived glioma cell cultures.
Our findings demonstrate a novel Wnt/β-catenin-miR-30a-5p-NCAM regulatory axis which plays important roles in controlling glioma cell invasion and tumorigenesis.
Wnt activity, evidenced by nuclear β-catenin in our cohort and high expression of its target AXIN2 (axis inhibitor protein 2) in published glioma datasets, was associated with shorter patient survival, although this was not statistically significant.
Consistently, MAGI3 overexpression in glioma cells C6 suppressed expression of β-catenin target genes including Cyclin D1 and Axin2, whereas MAGI3 knockdown in glioma cells U373 and LN229 enhanced their expression.