Erratum: Dihydroartemisinin inhibits the Raf/ERK/MEK and PI3K/AKT pathways in glioma cells.

[This corrects the article DOI: 10.3892/ol.2015.3699.].

An allele of rs619586 polymorphism in MALAT1 alters the invasiveness of meningioma via modulating the expression of collagen type V alpha (COL5A1).

The rs619586 polymorphism has been shown to alter the expression of MALAT1, which act as a competing endogenous RNA (ceRNA) against miR-145. And miR-145 was found to target COL5A1, the interaction between which was shown to be involved in the pathogenesis of invasive meningioma. In this study, we aimed to explore the effect of rs619586 polymorphism and its underlying molecular mechanism in invasive meningioma. Real-time PCR and Western Blot analysis were used to study the differentiated expression of miR-145, MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) and COL5A1 (collagen alpha-1(V) chain) in tumour/serum samples genotyped as rs619586 AA, AG and GG. Computational analysis and luciferase reporter assay were also conducted to identify the regulatory relationship between miR-145 and MALAT1/COL5A1. Meanwhile, expression of miR-145 and COL5A1 in different cell treatment groups was measured to validate the results obtained from earlier experiments. As shown by the results and in tumour/serum samples genotyped as AA, AG and GG, the expression of both MALAT1 and COL5A1 was down-regulated in a stepwise fashion, while the expression of miR-145 was increased, suggesting a potential negative relationship between MALAT1/COL5A1 and miR-145. Meanwhile, miR-145 was shown to bind to MALAT1, while COL5A1 was identified as a virtual target gene of miR-145. As a consequence, a MALAT1/miR-145/COL5A1 molecular pathway was established based on the above results. In particular, with the presence of rs619586 A>G polymorphism, the expression of MALAT1 and COL5A1 was both reduced, leading to reduced invasiveness of meningioma.

The expression of ATF3, MMP-2 and maspin in tissue chip of glioma.

This paper tested and analyzed the expression of ATF3 (activating transcription factor), MMP-2 (matrix metalloprotease) and maspin in tissue chip of glioma and its correlation with glioma advancement. Based on immunohistochemical staining, this paper selected 100 patients with glioma and 13 healthy persons to test the relative expression of ATF3, MMP-2 and maspin. The result witnessed 72.0% of ATF3 expression in glioma and 15.4% in healthy brain tissues with P<0.05; glioma had 76.0% of MMP-2 expression while healthy brain tissues only had 7.7% (P<0.05); but maspin expression with 53.0% in glioma was much lower than that with 100% in healthy tissues with P<0.05. If the pathological stage of glioma rose up, the expression of ATF3 and MMP-2 accordingly increased while maspin expression decreased. The correlation between ATF3 expression and MMP-2 expression was positive with r=0.553 and p<0.01; negative correlation between ATF3 expression and maspin expression was found with r=-0.457 and p<0.01; and the expression of MMP-2 and maspin were negatively related with r=-0.551 and p<0.01. According to the above results, it could be concluded that the expression of ATF3, MMP-2 and maspin did relate with each other. Besides, the high expression of ATF3 and MMP-2 as well as the low expression of maspin had great influence on glioma, playing a key role in glioma's occurrence, advancement, invasion and metastasis.

Decreased FOXD3 Expression Is Associated with Poor Prognosis in Patients with High-Grade Gliomas.

BACKGROUND: The transcription factor forkhead box D3 (FOXD3) plays important roles in the development of neural crest and has been shown to suppress the development of various cancers. However, the expression and its potential biological roles of FOXD3 in high-grade gliomas (HGGs) remain unknown. METHODS: The mRNA and protein expression levels of FOXD3 were examined using real-time quantitative PCR and western blotting in 23 HGG and 13 normal brain samples, respectively. Immunohistochemistry was used to validate the expression FOXD3 protein in 184 HGG cases. The association between FOXD3 expression and the prognosis of HGG patients were analyzed using Kaplan-Meier survival curves and Cox proportional hazards regression models. In addition, we further examined the effects of FOXD3 on the proliferation and serum starvation-induced apoptosis of glioma cells. RESULTS: In comparison to normal brain tissues, FOXD3 expression was significantly decreased in HGG tissues at both mRNA and protein levels. Immunohistochemistry further validated the expression of FOXD3 in HGG tissues. Moreover, low FOXD3 expression was significantly associated with poor prognosis in HGG patients. Depletion of FOXD3 expression promoted glioma cell proliferation and inhibited serum starvation-induced apoptosis, whereas overexpression of FOXD3 inhibited glioma cell proliferation and promoted serum starvation-induced apoptosis. CONCLUSIONS: Our results indicated that FOXD3 might serve as an independent prognostic biomarker and a potential therapeutic target for HGGs, which warrant further investigation.

Activating transcription factor 3 is overexpressed in human glioma and its knockdown in glioblastoma cells causes growth inhibition both in vitro and in vivo.

Glioblastomas are highly malignant gliomas that are extremely invasive with high rates of recurrence and mortality. It has been reported that activating transcription factor 3 (ATF3) is expressed in elevated levels in multiple malignant tumors. The purpose of this study was to investigate the function of ATF3 in the development of glioma and its clinical significance. Immunohistochemical staining, western blot analysis and RT-qPCR revealed that the mRNA and protein levels of ATF3 and matrix metalloproteinase 2 (MMP2) were higher in the glioma than in the normal human brain tissues, and that their levels were proportional to the pathological grades. By contrast, the mRNA and protein levels of mammary serine protease inhibitor (maspin; SERPINB5) were significantly lower in the glioma than in the normal brain tissue, and maspin expression was inversely proportional to the glioma pathological grade. The transfection of U373MG glioblastoma cells with ATF3-siRNA induced a number of changes in cell behavior; the cell proliferative activity was decreased and flow cytometry revealed an increased proportion of cells arrested in the G0/G1 phase of the cell cycle. In addition, TUNEL staining indicated an increased proportion of cells undergoing apoptosis and Transwell assays revealed impaired cell mobility. The sizes of the tumors grown as xenografts in nude mice were also significantly reduced by treatment of host mice with ATF3-siRNA. Taken together, these results suggest that ATF3 promotes the progression of human gliomas.

Clinical research for curing ankylosing spondylitis through combining etanercept, thalidomide and sulfasalazine.

This article is to explore the curative effect of treating ankylosing spondylitis (AS) through combining etanercept, thalidomide and sulfasalazine. Sixty-two patients with AS were divided into 3 groups: experimental group Ais treated by etanercept+ thalidomide + sulfasalazine for 1 year (n=22); control group B was treated with etanercept; control group C was treated with thalidomide + sulfasalazine for 1 year (n=20). In 1st, 3rd, 6th, 12th month after the treatment, ASAS20 and ASAS50 were obtained through Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), erythrocyte sedimentation rate (ESR), C react protein (CRP) and then curative effect was analyzed. In 1 and 3 months after the treatment, each indicator had downtrend, and ASAS20 of experimental group and etanercept control group reached 100%; ASAS50 increased compared with the first months' treatment; although ASAS20 and ASAS50 in thalidomide control group was smaller, they increased; in 6 and 12 months after the treatment, ASAS20 improvement ratio in group A still remained on 100%, ASA50 improvement ratio increased; recurrence rate of group B increased; ASA20 and ASA50 had a continuous and significant increase, but its their was less than group A. This study proved that, the effect of curing AS combiningetanercept, thalidomide and sulfasalazine is better, therefore, it is a high-feasible treatment approach.

Dihydroartemisinin inhibits the Raf/ERK/MEK and PI3K/AKT pathways in glioma cells.

It has previously been reported that dihydroartemisinin (DHA) is an effective novel anticancer compound in a number of types of tumor cells. Previous studies have demonstrated the anticancer activity of DHA in gioma cells. However, its underlining mechanism remains unclear. In the present study, the anticancer activity of DHA was examined in the glioma cell lines BT325 and C6. Western blot analysis was also employed to determine the signaling pathway changes. It was demonstrated that DHA effectively inhibited cell growth and induced apoptosis in glioma cells. Moreover, western blot analysis indicated that DHA-induced apoptosis was accompanied by inactivation of the Raf/MEK/ERK and PI3K/AKT signaling pathways, in addition to the downregulation of anti-apoptotic proteins Mcl-1 and Bcl-2 expression levels.