Scutellarin inhibits the metastasis and cisplatin resistance in glioma cells.

BACKGROUND: Scutellarin is a natural flavone compound that possesses anti-tumor and chemosensitization effects in several cancers. However, the effects of scutellarin on metastasis and chemoresistance in glioma have not been illustrated. METHODS: Glioma cells were treated with scutellarin in the presence or absence of LY294002. Cell proliferation was measured using a Cell Proliferation BrdU ELISA kit. Cell migration and invasion were analyzed using transwell assay. The expressions of E-cadherin, N-cadherin, vimentin, p-PI3K, PI3K, p-AKT, AKT, p-mTOR and mTOR were measured using Western blot. Furthermore, cells were incubated in the presence of cisplatin with or without the pretreatment of scutellarin. Cell viability was detected by the MTT assay. Cell apoptosis was measured using a histone/DNA ELISA detection kit. The expressions of ABCB1 and ABCG2 were detected using Western blot. RESULTS: In the present study, we found that scutellarin inhibited the proliferation, migration, and invasion of glioma cells. Scutellarin induced E-cadherin expression and reduced the expressions of N-cadherin, and vimentin in glioma cells. Our results also revealed that scutellarin enhanced chemosensitivity to cisplatin, as evidenced by the decreased cell viability to cisplatin and induced cell apoptosis. Moreover, scutellarin inhibited the expressions of ATP-binding cassette subfamily B member 1 and ATP-binding cassette sub-family G member 2 in cisplatin-resistant glioma cells. Scutellarin also prevented the activation of phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin pathway. CONCLUSION: The data suggested that scutellarin suppressed metastasis and chemoresistance in glioma cells. Scutellarin might be a new therapeutic approach for the glioma therapy.

Retracted Article: TRIM22 functions as an oncogene in gliomas through regulating the Wnt/ß-catenin signaling pathway.

The tripartite motif-containing (TRIM) family is a group of proteins that are implicated in a plethora of pathological conditions. TRIM22 has been found to be involved in various cancers; however, the role of TRIM22 in gliomas has not been reported. The present study aimed to evaluate the expression pattern of TRIM22 and its function in gliomas. TRIM22 expressions in glioma tissues and cell lines were measured by RT-PCR and western blot analysis. To knockdown TRIM22 by small hairpin RNAs (shTRIM22), the U118 cells were transfected with pLKO.1-shTRIM22 plasmid or pLKO.1 plasmid. Cell proliferation was measured using CCK-8 assay. Transwell assays were performed to evaluate the migration and invasion. The epithelial-mesenchymal transition (EMT) was assessed by detecting the expressions of E-cadherin, N-cadherin and vimentin with western blot analysis. A xenograft mouse model was established to evaluate the effect of TRIM22 silencing on tumor growth in vivo. The expressions of ß-catenin, cyclin D1, and c-Myc were analyzed by western blot analysis. TRIM22 was significantly overexpressed in glioma tissues and cell lines. In vitro studies demonstrated that TRIM22 knockdown inhibited cell proliferation, migration, and invasion. Additionally, TRIM22 silencing increased the expressions of E-cadherin, and decreased the expressions of N-cadherin and vimentin. Nude mouse xenograft assay showed that TRIM22 silencing inhibited tumor growth in vivo. Furthermore, silencing of TRIM22 inhibited the activation of the Wnt/ß-catenin pathway. Treatment with LiCl, an activator of the Wnt/ß-catenin pathway, attenuated the effects of shTRIM22 on U118 cells. Silencing of TRIM22 inhibited proliferation, migration and invasion, as well as repressing the EMT process in glioma cells. The Wnt/ß-catenin pathway was involved in the effect of TRIM22.

Knockdown of TRIM37 suppresses the proliferation, migration and invasion of glioma cells through the inactivation of PI3K/Akt signaling pathway.

Tripartite motif 37 (TRIM37), a member of the TRIM protein family, was involved in the tumorigenesis of several types of cancer. However, the expression pattern and role of TRIM37 in glioma remain unclear. Therefore, the aim of the present study was to investigate the role of TRIM37 in glioma, and to determine the molecular mechanisms. Our results demonstrated that TRIM37 was highly expressed in human glioma tissues and cell liens. Additionally, knockdown of TRIM37 dramatically inhibited the proliferation, migration/invasion, and the epithelial-mesenchymal transition (EMT) phenotype in glioma cells. Furthermore, knockdown of TRIM37 significantly reduced the levels of phosphorylated PI3K and Akt in U87MG cells, and an activator of PI3K/Akt signaling (SC79) partly reversed the inhibitory effects of si-TRIM37 on glioma cell proliferation and migration. Taken together, our results demonstrated that TRIM37 functions as an oncogene in the development and progression of glioma. TRIM37 knockdown inhibited the proliferation and invasion of human glioma cells at least in part through the inactivation of PI3K/Akt signaling pathway.

PAQR3 inhibits the proliferation, migration and invasion in human glioma cells.

Progestin and AdipoQ Receptor 3 (PAQR3), a member of the PAQR family, is down-regulated in several types of cancers and has been closely associated with tumor progression and development. However, little is known about the functions of PAQR3 in the tumorigenesis of human glioma. Therefore, in this report, we investigated the role of PAQR3 in human glioma. Our results showed that the expression of PAQR3 was significantly reduced in human glioma tissues and cell lines. PAQR3 overexpression inhibited the proliferation of glioma cells in vitro and attenuated tumor xenograft growth in vivo. In addition, PAQR3 overexpression suppressed the migration and invasion of glioma cells, as well as prevented the EMT process. Mechanistic studies demonstrated that PAQR3 overexpression significantly down-regulated the levels of phosphorylated PI3K and Akt in U251 cells. In conclusion, these results demonstrated that PAQR3 inhibited the proliferation, migration and invasion in glioma cells, at least in part, through the inactivation of PI3K/Akt signaling pathway. Therefore, PAQR3 may be a therapeutic target for the treatment of glioma.

Wnt/ß-catenin up-regulates Midkine expression in glioma cells.

Midkine, also known as neurite growth-promoting factor 2 (NEGF2), plays an important role in cell proliferation, apoptosis and differentiation. Recent studies have shown that Midkine is up-regulated in several types of human cancers. However, the molecular mechanism for its up-regulation remains poorly understood. Activation of Wnt/ß-catenin signaling is viewed as crucial for multiple tumor growth and metastasis, including glioma. In the present study, we found that Wnt3a administration or transfection of a constitutively activated ß-catenin promoted Midkine expression in glioma cells. We further identified a TCF/LEF binding site, with which beta-catenin interacts, on the proximal promoter region of Midkine gene, by luciferase reporter and chromatin immunoprecipitation assays. Thus, our results suggest a previously unknown Wnt/ß-catenin/Midkine molecular network controlling glioma development.

MicroRNA-214 targets PCBP2 to suppress the proliferation and growth of glioma cells.

PCBP2, a member of the poly(C)-binding protein (PCBP) family, is involved in posttranscriptional and translational regulation by interacting with single-stranded poly(C) motifs in target mRNAs. Recent studies have shown that PCBP2 is overexpressed and plays an important role in human cancers, including glioma. However, the molecular basis for its up-regulation remains poorly understood. Here, we show that microRNA-214 (miR-214) interacts with the 3'-untranslated region of PCBP2 mRNA and induces its degradation, leading to reductions in its protein expression. As a result, overexpression of miR-214 mimics significantly inhibited, while its antisense oligos proliferation and growth of glioma cells. Restoration of PCBP2 remarkably reversed the tumor-suppressive effects of miR-214 on cell proliferation and growth. In summary, our data indicate that miR-214 may function as tumor suppressor in glioma by targeting PCBP2.