[Retracted] 14­3­3ß exerts glioma­promoting effects and is associated with malignant progression and poor prognosis in patients with glioma.

[This retracts the article DOI: 10.3892/etm.2017.5664.].

[Retracted] Knockdown of PREX2a inhibits the malignant phenotype of glioma cells.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that cell invasion assay data in the article (featured in Fig. 4A) were strikingly similar to data appearing in different form in another article by different authors at different research institutions, which had already been published elsewhere at the time of the present article's submission. Furthermore, flow cytometric data featured in Fig. 2D were strikingly similar to those in another previously published paper, and cell cyle data included in Fig. 3 had apparently previously published elsewhere. Owing to the fact that the contentious data in the above article had already appeared in different form in other articles prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors also expressed their intention to retract the paper on the grounds that the corresponding author and several of the authors failed to confirm the approval of the final version of the manuscript. The Editor apologizes to the readership for any inconvenience caused. [the original article was published on Molecular Medicine Reports 13: 2301­2307, 2016; DOI: 10.3892/mmr.2016.4799].

Gambogic Acid Affects Ribosomal Occurrence in Glioma Cells by Downregulating the Phosphoinositide Kinase-3/Protein Kinase B/Mammalian Target of Rapamycin Signaling Pathway.

Gambogic acid (GA) is a natural compound with a polyprenylated xanthone structure that has antiinflammatory, antioxidant, and neuroprotective properties and acts as a chemopreventive agent. GA exhibits anti-tumor, antimicrobial, and anti-proliferative effects on cancer cells. In the current study, the effect of GA on phosphoinositide kinase-3 (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway was examined in human U251 glioma cells. Cell viability and apoptosis were evaluated by MTT and Annexin V/PI Double Staining. The expressions of P38, AKT, and mTOR were evaluated by western blot and qRT-PCR, respectively. MagBeads Total RNA Extraction Kit was used to isolate cell tissue RNA. GA decreased the phosphorylation of P38, AKT, and mTOR. Inhibitors of PI3K (LY294002) enhanced the phosphorylation of P38, AKT, and mTOR. GA reduced the phosphorylation of ribosomal protein precursors (Pre) and upstream binding factor (UBF), and insulin-like growth factor I (IGF-1) further enhanced the cell proliferation and expression of Pre and UBF. These results suggested that downregulation of PI3K/AKT/mTOR signaling pathway may be an important mediator in GA-affected ribosomal occurrence in glioma cells.

14-3-3ß exerts glioma-promoting effects and is associated with malignant progression and poor prognosis in patients with glioma.

Glioma is a type of tumor that affects the central nervous system. It has been demonstrated that 14-3-3ß, a protein that is mainly concentrated in the brain, serves an important role in tumor regulation. However, the mechanism of action of 14-3-3ß that underlies the pathogenesis of glioma remains to be elucidated. In the present study, 14-3-3ß was silenced by RNA interference in the human glioma cell line U373-MG. Following knockdown of 14-3-3ß, the proliferation, colony formation, cell cycle progression, migration and invasion of U373-MG cells were significantly decreased (P<0.01), whereas cell apoptosis was increased (P<0.01). Furthermore, in a tumor xenograft experiment, silencing 14-3-3ß significantly inhibited the in vivo tumor growth of U373-MG cells (P<0.01). The results demonstrated that 14-3-3ß levels were significantly higher in human glioma tissues compared with normal brain tissues (P<0.01) and high 14-3-3ß expression was significantly associated with advanced pathological grade (P<0.03) and low Karnofsky performance scale (P<0.003). Patients with glioma who had high 14-3-3ß levels had a significantly shorter survival time compared with those with low expression of 14-3-3ß (P=0.031), suggesting that 14-3-3ß may be an effective predictor of the prognosis of patients with glioma. The results of the present study indicate that 14-3-3ß serves an oncogenic role in glioma, suggesting that 14-3-3ß may have potential as a promising therapeutic target for glioma.

Knockdown of PREX2a inhibits the malignant phenotype of glioma cells.

Glioma is the most common type of malignant brain tumor. Phosphatidylinositol­3,4,5­trisphosphate­dependent Rac exchange factor 2a (PREX2a), which is a regulator of the small guanosine triphosphatase Rac, has previously been identified as an oncoprotein that inhibits phosphatase and tensin homolog deleted on chromosome 10 (PTEN) activity. However, the role of PREX2a in the regulation of the malignant phenotype of glioma has yet to be reported. The present study demonstrated that the mRNA and protein expression levels of PREX2a were significantly increased in glioma tissue, as compared with in normal brain tissue. Furthermore, the expression levels of PREX2a were positively correlated with tumor grade. PREX2a­specific small interfering RNA­mediated knockdown significantly inhibited proliferation and induced apoptosis of SWO­38 glioma cells. Furthermore, inhibition of PREX2a expression significantly suppressed cell cycle progression in glioma cells, as detected by cell cycle arrest at G1 phase. In addition, knockdown of PREX2a inhibited the invasion of SWO­38 glioma cells. The present study also investigated the molecular mechanisms underlying the effects of PREX2a knockdown, and demonstrated that phosphoinositide 3­kinase signaling was significantly downregulated, which may be due to the upregulation of PTEN activity. In conclusion, the present study is the first, to the best of our knowledge, to suggest that knockdown of PREX2a may effectively inhibit the malignant phenotype of glioma in vitro; therefore, PREX2a may be considered a potential molecular target for the treatment of glioma.

Autophagy inhibition promotes gambogic acid-induced suppression of growth and apoptosis in glioblastoma cells.

OBJECTIVE: To investigate the effects of gambogic acid (GA) on the growth of human malignant glioma cells. METHODS: U251MG and U87MG human glioma cell lines were treated with GA and growth and proliferation were investigated by MTT and colony formation assays. Cell apoptosis was analyzed by annexin V FITC/PI flow cytometry, mitochondrial membrane potential assays and DAPI nuclear staining. Monodansylcadaverine (MDC) staining and GFP-LC3 localisation were used to detect autophagy. Western blotting was used to investigate the molecular changes that occurred in the course of GA treatment. RESULTS: GA treatment significantly suppressed cell proliferation and colony formation, induced apoptosis in U251 and U87MG glioblastoma cells in a time- and dose-dependent manner. GA treatment also lead to the accumulation of monodansylcadaverine (MDC) in autophagic vacuoles, upregulated expressions of Atg5, Beclin 1 and LC3-II, and the increase of punctate fluorescent signals in glioblastoma cells pre-transfected with GFP-tagged LC3 plasmid. After the combination treatment of autophagy inhitors and GA, GA mediated growth inhibition and apoptotic cell death was further potentiated. CONCLUSION: Our results suggested that autophagic responses play roles as a self-protective mechanism in GA-treated glioblastoma cells, and autophagy inhibition could be a novel adjunctive strategy for enhancing chemotherapeutic effect of GA as an anti-malignant glioma agent.