Expression In Glioma Tissues Research Articles

MicroRNA-770 affects proliferation and cell cycle transition by directly targeting CDK8 in glioma

BackgroundMicroRNAs play crucial roles in tumorigenesis and tumor progression. miR-770 has been reported to be downregulated in several cancers and affects cancer cell proliferation, apoptosis, metastasis and drug resistance. However, the role and underlying molecular mechanism of miR-770 in human glioma remain unknown and need to be further elucidated.MethodsThe expression of miR-770 in glioma tissues and cell lines was measured by quantitative real-time PCR (qRT-PCR) to explore the association of miR-770 expression with clinicopathological characteristics. The expression of CDK8 was detected by qRT-PCR and Western blotting in glioma tissues. A target prediction program and a dual-luciferase reporter assay were used to confirm that CDK8 is a target gene of miR-770. MTT and cell counting assays were used to assess the effect of miR-770 on glioma cell proliferation. The cell cycle distribution and apoptosis were examined by flow cytometry. CDK8 siRNA and overexpression were used to further confirm the function of the target gene.ResultsWe demonstrated that miR-770 expression was downregulated in human glioma tissues and cell lines. The overexpression of miR-770 inhibited glioma cell proliferation and cell cycle G1-S transition and induced apoptosis. The inhibition of miR-770 facilitated cell proliferation and G1-S transition and suppressed apoptosis. miR-770 expression was inversely correlated with CDK8 expression in glioma tissues. CDK8 was confirmed to be a direct target of miR-770 by using a luciferase reporter assay. The overexpression of miR-770 decreased CDK8 expression at both the mRNA and protein levels, and the suppression of miR-770 increased CDK8 expression. Importantly, CDK8 silencing recapitulated the cellular and molecular effects observed upon miR-770 overexpression, and CDK8 overexpression eliminated the effects of miR-770 overexpression on glioma cells. Moreover, both exogenous expression of miR-770 and silencing of CDK8 resulted in suppression of the Wnt/β-catenin signaling pathway.ConclusionsOur study demonstrates that miR-770 inhibits glioma cell proliferation and G1-S transition and induces apoptosis through suppression of the Wnt/β-catenin signaling pathway by targeting CDK8. These findings suggest that miR-770 plays a significant role in glioma progression and serves as a potential therapeutic target for glioma.

MicroRNA‑940 promotes cell proliferation and invasion of glioma by directly targeting Kruppel‑like factor9.

MicroRNA‑940 (miR‑940) has been extensively studied in the pathogenesis of numerous types of human cancer; however, the expression pattern, roles and molecular mechanisms underlying the regulatory actions of miR‑940 in glioma remain unknown. The present study aimed to further investigate miR‑940 by studying its expression, roles and mechanisms of action in glioma. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was used to detect miR‑940 expression in glioma tissues and cell lines. The regulatory effects of miR‑940 in glioma cell proliferation and invasion were determined using MTT and cell invasion assays. Bioinformatics analyses was performed to identify the potential target of miR‑940, which was further confirmed by luciferase reporter assay, RT‑qPCR and western blot analysis. In the present study, significantly increased miR‑940 expression levels were observed in glioma tissues and cell lines compared with normal brain tissues and normal human astrocytes, respectively. Decreased miR‑940 expression levels attenuated glioma cell proliferation and invasion invitro. Kruppel‑like factor9 (KLF9) was predicted as a potential target of miR‑940. Further assays demonstrated that miR‑940 negatively regulated KLF9 expression in glioma cells by directly targeting the 3'‑untranslated regions of KLF9. Additionally, KLF9 expression was downregulated in glioma tissues and was inversely correlated with miR‑940. Furthermore, KLF9 knockdown was able to rescue the effects of miR‑940 on glioma cell proliferation and invasion. The results of the present study suggest that miR‑940 may function as an oncogene in glioma by targeting KLF9 and may be a considered a therapeutic target for the treatment of gliomas.

Circular RNA hsa_circ_0074362 Promotes Glioma Cell Proliferation, Migration, and Invasion by Attenuating the Inhibition of miR-1236-3p on HOXB7 Expression.

As a novel type of noncoding RNAs, circular RNAs (circRNAs) have been acknowledged as pivot effectors in multiple physiological and pathological processes, including cancer. Although an increasing number of circRNAs are gradually discovered, their function and mechanism in tumorigenesis remain largely unknown. In this study, we identified hsa_circ_0074362 as an oncogene in glioma. We examined hsa_circ_0074362 expression in glioma tissues and cell lines by qRT-PCR and investigated its functions by using CCK8 and transwell assays. Luciferase reporter assays were conducted to confirm the interaction between miR-1236-3p and hsa_circ_0074362 or HOXB7. Results demonstrated that hsa_circ_0074362 was significantly upregulated in glioma tissues compared with normal tissues, and hsa_circ_0074362 overexpression was correlated with clinical severity and poor prognosis in patients with glioma. Moreover, hsa_circ_0074362 knockdown remarkably suppressed glioma cell proliferation, migration, and invasion. Luciferase reporter assay indicated that hsa_circ_0074362 acted as a sponge of miR-1236-3p to promote HOXB7 expression. Thus, hsa_circ_0074362 played a crucial role in glioma progression by regulating the miR-1236-3p/HOXB7 pathway.

Regulation of mTOR by miR-107 to facilitate glioma cell apoptosis and to enhance cisplatin sensitivity.

The aberrant increasing expression of mammalian target of rapamycin (mTOR) participates in tumor occurrence and drug resistance. It has been found elevation of mTOR expression but reducing miR-107 expression in glioma tissues. Thus, we investigated the regulatory role of miR-107 on mTOR expression as well as glioma cell proliferation, apoptosis and cisplatin (DDP) resistance. Dual luciferase reporter gene assay was applied to confirm targeted regulation between miR-107 and mTOR. Tumor tissues were collected from glioma patients, in parallel with normal tissues after brain contusion surgery. Expressions of miR-107, mTOR and p-mTOR were compared. DDP-resistant cell line U251/DPP was generated. U251/DPP cells were further treated with miR-107 mimic or si-mTOR to examine the change of miR-107, mTOR, p-mTOR and survivin levels. Flow cytometry was used to quantify the effect of DDP treatment on cell proliferation or apoptosis. Bioinformatics analysis revealed complementary binding sites between miR-107 and 3'-UTR of mTOR mRNA. Dual luciferase assay confirmed targeted regulation between miR-107 and mTOR. Compared to control group, in glioma tissues, mTOR and p-mTOR expressions were significantly elevated, while the level of miR-107 expression was markedly decreased. Of note, U251/DDP cells presented weakened apoptosis compared to U251 cells, with high levels of mTOR, p-mTOR and survivin and reduction of miR-107 expression. However, the transfection of miR-107 mimic and/or si-mTOR remarkably suppressed expressions of mTOR, p-mTOR and survivin in U251/DPP cells, weakened cell proliferation and enhanced apoptosis. We demonstrated that the level of miR-107 was correlated with DDP resistance in glioma cells. Over-expression of miR-107 decreased DPP resistance of glioma cells via inhibition of mTOR, which provides academic basis for the future anti-glioma therapy.

MicroRNA-200b expression level is negatively associated with pathological grading in human gliomas.

AimTo elucidate the clinical implication of microRNA (miRNA)-200b in the pathological grading of gliomas.MethodsWe searched the Chinese National Knowledge Infrastructure, Web of Knowledge, Embase, and PubMed databases. Related articles were assessed, and ORs with 95% CIs were calculated to examine the relationship between miRNA-200b expression levels and the World Health Organization (WHO) glioma grade, patients’ sex and age, tumor size, and extent of surgical resection. Heterogeneity, publication bias, and stability of the pooled results of the included studies were also analyzed. MiR-200b expression in 87 human glioma tissues (50 high grade and 37 low grade) and matched 41 non-neoplastic brain tissues was measured by real-time quantitative RT-PCR assay.ResultsFive eligible studies involving 630 patients were included in the present meta-analysis. The miRNA-200b expression in glioma tissues was negatively associated with the WHO glioma grade (OR, 0.070; 95% CI, 0.007–0.678; P=0.022). No significant correlations were found between miRNA-200b and sex (P=0.858), age (P=0.776), tumor size (P=0.134), or extent of resection (P=0.778). In our own test, compared with non-neoplastic brain tissues, the expression level of miR-200b was significantly decreased in glioma tissues (tumor vs normal: 4.29±1.90 vs 10.45±2.34, P<0.001). In addition, we found that the glioma tissues from high-grade tumors (grade III and IV) had much lower miR-200b expression than glioma tissues from low grade tumors (grade I and II).ConclusionOur results suggest that the miRNA-200 expression level may be negatively associated with the WHO glioma grade (malignancy). MiRNA-200 might serve as a prognostic and diagnostic biomarker or a helpful therapeutic target.

MiRNA-93 functions as an oncogene in glioma by directly targeting RBL2.

Glioma is a tumor of the brain. Although the clinical regimens and surgical techniques for glioma have improved, therapies of advanced glioma remain challenging, carrying dismal overall survival and therapeutic success rates. Evidence has shown that miRNAs played important roles in glioma development. The current study aimed at investigating the function of a novel cancerogenic miRNA, miR-93, in glioma progression by investigating the expression and mechanism of it. qRT-PCR was conducted to assess the miR-93 expression and the mRNA expression of target gene in glioma tissues and cells. The invasion and migration abilities of the glioma cells were determined by transwell assays. Luciferase reporter assay was performed to confirm the target of miR-93. The results indicated that miR-93 expression in glioma tissues and cells was increased significantly than that in normal brain tissues and cells. Furthermore, miR-93 promoted glioma cell migration and invasion. RBL2 was recognized as a direct target of miR-93 in glioma cells, and overexpression of RBL2 could reverse the stimulative effect of miR-93 in glioma cell. The above findings suggested that miR-93 together with RBL2 could be diagnostic targets and novel prognostic markers for glioma.

Role of miR-613 as a tumor suppressor in glioma cells by targeting SOX9.

Background and objectivesMicroRNA-613 (miR-613), a novel cancer-related microRNA, has been shown to be responsible for the inhibition of tumor development and progression in various cancers. We aimed to investigate the biological function and regulatory mechanisms of miR-613 in gliomas.Materials and methodsmiR-613 expression were detected by qRT-PCR assays in glioma tissues and cell lines. Cell Counting Kit-8 (CCK-8) assay, colony formation analysis, wound healing and transwell invasion assays were performed to evaluate cell proliferation, colony formation, migration and invasion abilities. Luciferase reporter assays, qRT-PCR and Western blot were performed to explore the potential targets of miR-613. Xenograft mice model was established to evaluate the effect of miR-613 in vivo.ResultThe expression levels of miR-613 were significantly downregulated in the glioma tissues and cell lines, and the decreased level was significantly negatively associated with the overall disease-free survival of the patients. Functionally, ectopic expression of miR-613 in glioma cells suppressed the proliferation, colony formation, and migration and invasion of the cells. The sex-determining region Y-box 9 (SOX9) was identified as a direct functional target of miR-613, and its expression was inversely correlated with miR-613 expression in glioma tissues. Moreover, rescue of SOX9 could partially reverse the inhibitory effects of miR-613 on glioma cell proliferation, colony formation, migration, and invasion. Importantly, miR-613 also suppressed tumor growth in vivo by targeting SOX9.ConclusionTaken together, these findings demonstrate that miR-613 functions as a tumor suppressor in glioma cells by directly targeting SOX9.

Knockdown of Long Noncoding RNA LUCAT1 Inhibits Cell Viability and Invasion by Regulating miR-375 in Glioma.

Recently, long noncoding RNAs (lncRNAs) have emerged as new gene regulators and prognostic markers in several cancers, including glioma. Here we focused on lncRNA LUCAT1 on the progression of glioma. qRT-PCR was used to determine the expression of LUCAT1 and miR-375 in glioma tissues and cells. MTT and Transwell invasion assays were performed to determine the function of LUCAT1 in glioma progression. The bioinformatics tool DIANA was used to predict the targets of LUCAT1. Pearson’s correlation analysis was performed to explore the correlation between LUCAT1 and miR-375. In the present study, we showed that LUCAT1 was substantially upregulated in glioma tissues and cells. LUCAT1 inhibition significantly suppressed the proliferation and invasion of glioma cells. Subsequently, DIANA showed that miR-375 was predicted to contain the complementary binding sites to LUCAT1. Luciferase reporter assay showed that miR-375 directly targeted LUCAT1. In addition, we found that miR-375 was downregulated in glioma tissues and negatively correlated with LUCAT1 expression in glioma tissues. Furthermore, the results showed that miR-375 could rescue the function of LUCAT1 in glioma progression. The lncRNA LUCAT1 was critical for the proliferation and invasion of glioma cells by regulating miR-375. Our findings indicated that LUCAT1 might offer a potential novel therapeutic target for the treatment of glioma.

Tumor suppressor candidate 3: A novel grading tool and predictor of clinical malignancy in human gliomas.

For several years, the cause of autosomal recessive mental retardation has been attributed to the deletion or mutation of a gene named tumor suppressor candidate 3 (TUSC3). Previous research has identified that TUSC3 is a potential tumor suppressor gene in oral epidermoid carcinoma, lung cancer and esophageal cancer. However, to the best of our knowledge, no previously published data has existed on the expression of TUSC3 in gliomas. The present study focused on the expression of TUSC3 in brain gliomas. Additionally, the present study sought to identify he association between TUSC3 expression and the typical clinical and pathological disease manifestations of gliomas. TUSC3 levels were evaluated using a western blot assay and immunohistochemistry on tissue microarray slides. Results indicated a significant decrease in TUSC3 expression in glioma tissues compared with the normal adjacent tissues. Furthermore, TUSC3 expression and World Health Organization grade demonstrated an inverse association in patients with glioma. This revealed that lower levels of TUSC3 in gliomas may be associated with a poorly-differentiated (high grade) tumor and thus a higher malignancy. Through the combination of the results of the present study and future research projects, TUSC3 may be a novel grading tool that assists with evaluating tumor malignancy and consequently a more active therapeutic regimen may be used in patients with glioma.

Methylation-induced downregulation and tumor-suppressive role of microRNA-98 in glioma through targeting Sal-like protein 4.

MicroRNAs (miRs) have been found to play key roles in various human cancers, but the detailed regulatory mechanism of miR-98 in glioma remains largely unknown. The findings of the present study demonstrated that miR-98 was frequently downregulated in glioma tissues and cell lines (U87, U251, U373 and SHG44), and the decreased miR-98 levels were associated with DNA methylation. Treatment with 5-Aza-20-deoxycytidine, a DNA methyltransferase inhibitor, significantly increased the expression of miR-98 in glioma cells. Moreover, both miR-98 downregulation and methylation were significantly associated with a more aggressive tumor phenotype in glioma, as well as shorter survival time of glioma patients. Restoration of miR-98 expression caused a marked decrease in the migration and invasion of U87 cells, but did not affect cell proliferation. Sal-like protein 4 (SALL4) was further identified as a novel target gene of miR-98, and its protein expression was negatively regulated by miR-98 in U87 cells. Restoration of SALL4 expression reversed the suppressive effects of miR-98 on the migration and invasion of U87 cells. Furthermore, SALL4 was significantly upregulated in glioma tissues and cell lines, and an inverse correlation between miR-98 and SALL4 expression in glioma tissues was identified. In addition, the increased expression of SALL4 was significantly associated with glioma progression. Taken together, these data demonstrated that downregulation of miR-98, induced by methylation, promotes glioma cell migration and invasion via targeting SALL4. Therefore, miR-98 may become a potential therapeutic candidate for glioma.

Ubiquitin carboxyl-terminal hydrolase isozyme L5 inhibits human glioma cell migration and invasion via downregulating SNRPF.

Ubiquitin C-terminal Hydrolase-L5 (UCH-L5/UCH37), a member of the deubiquitinases (DUBs), suppresses protein degeneration via removing ubiquitin from the distal subunit of the polyubiquitin chain. The activity of UCH-L5 is enhanced when UCH-L5 combines with proteasome 19S regulatory subunit by Rpn13/Admr1 receptor and inhibited when UCH-L5 interacts with NFRKB. But the role of UCH-L5 in gliomas remains unknown. In this study, analysis of 19 frozen and 51 paraffin-embedded clinic pathological cases showed that UCH-L5 expression in glioma tissues was lower than normal brain tissues. In vitro, we found that UCH-L5 could inhibit migration and invasion of U87MG and U251 cells. It has been reported that the expression of SNRPN, SNRPF, and CKLF was abnormal in gliomas or other tumors. We also found that SNRPF-siRNA, SNRPN-siRNA and CKLF-siRNA could inhibit migration and invasion of U87MG cells. And knockdown of UCH-L5 expression improved both mRNA expression and protein level of SNRPF. The relationship between UCH-L5 and SNRPF was further confirmed in 293T cells. Our study showed that UCH-L5 could inhibit migration and invasion of glioma cells via down regulating expression of SNRPF. And the above findings suggest that UCH-L5 may inhibit occurrence and metastasis of gliomas.

BAF53a is a potential prognostic biomarker and promotes invasion and epithelial-mesenchymal transition of glioma cells.

Increasing evidence indicates that BAF53a is crucial for embryonic development and maintenance of stemness, and may be associated with epithelial-mesenchymal transition (EMT), which suggests its involvement in cancer progression. However, the role of BAF53a in glioma remains unknown. In the present study, BAF53a was found to be highly expressed in glioma tissues and was associated with poor overall survival (OS) and progression-free survival (PFS) in glioma patients. A multivariate Cox regression analysis revealed that BAF53a might be an independent prognostic factor for OS and PFS in glioma patients. Further functional analysis indicated that BAF53a overexpression could promote proliferation and increase the motility and invasion of U87 glioma cells, whereas BAF53a knockdown had the opposite effect. In addition, BAF53a expression was associated with the levels of E-cadherin and vimentin expression in glioma tissues. This was further confirmed in U87 cells expressing different levels of BAF53a; BAF53a overexpression was concomitant with decreased E-cadherin and increased vimentin expression, whereas BAF53a knockdown showed the opposite pattern of expression. Taken together, these results suggest that BAF53a may be a novel prognostic factor for glioma patients, and that BAF53 may facilitate glioma progression by promoting proliferation, invasion, and associate with EMT. Therefore, BAF53a could be a potential promising biomarker and a target for the treatment of glioma.

MiRNA-155 promotes proliferation by targeting caudal-type homeobox 1 (CDX1) in glioma cells

MicroRNAs (miRNAs) play important roles in the tumorigenesis of glioma. Recent studies showed that miR-155 expression was increased in types of cancer, including glioma. However, the underlying mechanism of miR-155 on glioma is still unclear. In the present study, expression of miR-155 and caudal-type homeobox 1 (CDX1) was determined in glioma tissues by qRT-PCR, and the regulatory axis was further studied in glioma cells. We showed that miR-155 expression was significantly increased in glioma tissues while CDX1 expression was decreased. Correlation analysis revealed that miR-155 was negatively correlated with CDX1 expression in glioma tissues. Moreover, Kaplan–Meier analysis indicated that patients with high miR-155 expression had a poor overall survival. In addition, our results showed that the translation of CDX1 expression could be suppressed by miR-155 mimics. And miR-155 mimics promoted glioma cell proliferation could be reversed by CDX1 overexpression. In vivo assay, we showed that miR-155 overexpression promoted the progress of tumor formation. Therefore, we suggested that miR-155 might promote glioma cell growth partially by targeting CDX1, which provided a novel therapeutic strategy for glioma patients.

Aberrant rhythmic expression of cryptochrome2 regulates the radiosensitivity of rat gliomas.

In this study, we investigated the role of the clock regulatory protein cryptochrome 2 (Cry2) in determining the radiosensitivity of C6 glioma cells in a rat model. We observed that Cry2 mRNA and protein levels showed aberrant rhythmic periodicity of 8 h in glioma tissues, compared to 24 h in normal brain tissue. Cry2 mRNA and protein levels did not respond to irradiation in normal tissues, but both were increased at the ZT4 (low Cry2) and ZT8 (high Cry2) time points in gliomas. Immunohistochemical staining of PCNA and TUNEL assays demonstrated that high Cry2 expression in glioma tissues was associated with increased cell proliferation and decreased apoptosis. Western blot analysis showed that glioma cell fate was independent of p53, but was probably dependent on p73, which was more highly expressed at ZT4 (low Cry2) than at ZT8 (high Cry2). Levels of both p53 and p73 were unaffected by irradiation in normal brain tissues. These findings suggest aberrant rhythmic expression of Cry2 influence on radiosensitivity in rat gliomas.

MiR-599 inhibits proliferation and invasion of glioma by targeting periostin.

To explore the molecular mechanism of microRNA-599(miR-599) in the migration and invasion of glioma. Clinicopathological characteristics of 33 patients were analyzed. Based on reverse transcription-PCR, miR-599 was down-regulated in glioma tissues compared with adjacent normal brain tissues (P<0.001). Moreover, negative correlations between miR-599 and periostin protein expression in glioma tissues (P<0.01) and necrosis by magnetic resonance imaging (P<0.05) were observed. Transwell and wound healing assays showed that overexpression of miR-599 inhibited glioma cell migration and invasion. miR-599 down-regulated periostin expression by targeting the 3'-untranslated region. Additionally, re-expression of periostin partial reversed the suppressive effect of miR-599 on migration and invasion in vitro and in vivo. microRNA-599 inhibits proliferation and invasion by down-regulating periostin expression in vitro and in vivo.

Retraction Note to: The Clinical Implications of Human Telomerase Reverse Transcriptase Expression in Grade and Prognosis of Gliomas: a Systematic Review and Meta-analysis.

Human telomerase reverse transcriptase (hTERT), a ribonucleoprotein, is reported as an important complex, which is required for stability of DNA molecular structure at the rear of the chromosome. Until now, hTERT has been linked to cell immortalization and tumorigenesis. A couple of articles have been published about the telomerase function in the gliomas; however, these results are conflicting in some degree. Thus, it is crucial to perform a meta-analysis to identify their real actions. We included eligible articles, and estimated odds ratios (ORs) with 95 % confidence intervals (95 % CIs). In our meta-analysis, all 15 eligible articles included 932 patients. Results from 10 studies on WHO grade showed that high hTERT gene or protein expression in glioma tissues was obviously related to high WHO grade (III + IV) (OR 2.45, 95 % CI 1.92–3.13; p = 0.000). What is more, hTERT expression was not associated with old age (OR 0.91, 95 % CI 0.72–1.16; p = 0.448) as well as gender (OR 1.06, 95 % CI 0.82–1.37; p = 0.664). Importantly, hTERT expression was significantly associated with 5-year overall survival (OS; n = 3; hazard ratio (HR) 2.25, 95 % CI 1.36–3.70; p = 0.002) of glioma patients. No heterogeneity was found in all studies. In conclusion, this meta-analysis suggests that hTERT is significantly associated with high glioma grade and poor 5-year overall survival, and pathological test of hTERT mRNA and protein in glioma tissues should be suggested as criteria of glioma grade in the clinical practice.

Identification of repaglinide as a therapeutic drug for glioblastoma multiforme

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with a median survival time of only 14 months after treatment. It is urgent to find new therapeutic drugs that increase survival time of GBM patients. To achieve this goal, we screened differentially expressed genes between long-term and short-term survived GBM patients from Gene Expression Omnibus database and found gene expression signature for the long-term survived GBM patients. The signaling networks of all those differentially expressed genes converged to protein binding, extracellular matrix and tissue development as revealed in BiNGO and Cytoscape. Drug repositioning in Connectivity Map by using the gene expression signature identified repaglinide, a first-line drug for diabetes mellitus, as the most promising novel drug for GBM. In vitro experiments demonstrated that repaglinide significantly inhibited the proliferation and migration of human GBM cells. In vivo experiments demonstrated that repaglinide prominently prolonged the median survival time of mice bearing orthotopic glioma. Mechanistically, repaglinide significantly reduced Bcl-2, Beclin-1 and PD-L1 expression in glioma tissues, indicating that repaglinide may exert its anti-cancer effects via apoptotic, autophagic and immune checkpoint signaling. Taken together, repaglinide is likely to be an effective drug to prolong life span of GBM patients.

Serpin peptidase inhibitor, clade A member 3 (SERPINA3), is overexpressed in glioma and associated with poor prognosis in glioma patients.

Glioma is the most common and aggressive human primary tumor in the central nervous system. Despite present clinical advancements, median survival time remains poor in this malignant tumor. Serpin peptidase inhibitor, clade A member 3 (SERPINA3), is a member of the serpin superfamily of protease inhibitors. Its aberrant expression has been observed in various tumors. However, its clinical significance and biological function in glioma remain unclear, especially for the prognosis of glioma patients. In this study, we investigated SERPINA3 expression in glioma tissue samples and its significance in predicting the prognosis of glioma patients. SERPINA3 protein expression was studied by immunohistochemistry, while real-time polymerase chain reaction was used to study SERPINA3 mRNA expression. We found that SERPINA3 was upregulated in glioma tissue at both mRNA and protein levels, compared with noncancerous brain tissues. We also found that high SERPINA3 expression in glioma tissues correlated significantly with advanced World Health Organization grade. Univariate and multivariate analyses revealed that high SERPINA3 expression was an independent prognostic factor for poor overall survival of glioma patients. Moreover, our findings were further validated by online Oncomine database. Taken together, our results suggest that SERPINA3 plays an oncogenic role in glioma progression and provide an insight into the application of SERPINA3 as a novel predictor of clinical outcomes and a potential biomarker of glioma.

MicroRNA-520c inhibits glioma cell migration and invasion by the suppression of transforming growth factor-β receptor type2.

Dysregulation of microRNAs (miRNAs) is actively involved in the development and progression of glioma. miR-520c was previously found to inhibit glioblastoma cell migration. However, the clinical significance of miR-520c and its biological function in glioma remain largely unknown. In the present study, we found that miR-520c expression in glioma tissues was significantly decreased compared to adjacent non‑cancerous tissues. The low level of miR-520c was prominently correlated with advanced World Health Organization (WHO) grade and decreased overall survival of glioma patients. Overexpression of miR-520c in U251 cells significantly decreased the migration and invasion of the cancer cells, while miR-520c silencing promoted U87 cell migration and invasion invitro. Mechanistically, miR-520c inversely regulated transforming growth factor-β receptor type 2(TGFBRII) abundance in the glioma cells. Herein, TGFBRII was found to be a downstream target of miR-520c in glioma. Furthermore, an inverse correlation between TGFBRII and miR-520c expression was observed in the glioma cases. In constrast, restoration of TGFBRII expression abrogated the effects of miR-520c overexpression in U251 cells with increased cell migration and invasion. In addition, miR-520c overexpression blocked TGF-β1‑induced cell migration and invasion in U251 cells. Collectively, miR-520c may serve as a prognostic predictor and a therapeutic target for gliomapatients.

Retraction Note to: The Clinical Implications of Transforming Growth Factor Beta in Pathological Grade and Prognosis of Glioma Patients: A Meta-Analysis.

The transforming growth factor beta (TGF-β) pathway plays a key role in oncogenesis of advanced cancers. However, the effects of TGF-β pathway on gliomas are still controversial. So, it is essential to conduct a meta-analysis to determine their correlations. Eligible studies were included, and then odds ratios (ORs), standard mean differences (SMDs), and hazard ratios (HRs) with 95 % confidence intervals (95 % CIs) were estimated. Funnel plots were available for evaluation of publication bias. In this meta-analysis, all 14 eligible studies involving 875 patients were included and conducted in China. Six studies with dichotomous data revealed altered TGF-β expression in glioma tissues was closely associated with high WHO grade (III + IV) (OR 4.39, 95 % CI 2.90–6.63; p = 0.000), meanwhile, seven studies with continuous data also demonstrated TGF-β expression intensity extremely related to high grade (SMD −2.44, 95 % CI −2.71, −2.16; p = 0.000). To our interest, TGF-β expression was associated with old age (OR 0.59, 95 % CI 0.36–0.93; p = 0.025) rather than gender (OR 1.04, 95 % CI 0.64–1.67; p = 0.884). Besides, TGF-β expression significantly correlated to 3-year-OS (n = 2; HR 2.53, 95 % CI 1.18–5.41; p = 0.017) rather than 5-year-OS (n = 1; HR 1.04, 95 % CI 0.66–1.64; p = 0.872) in glioma patients. No heterogeneity and publication bias were observed across all studies. Taken together, the present meta-analysis testifies TGF-β is potently associated with high grade and poor 3 years prognosis, and TGF-β test combined with survivin [1 Mol Neurobiol] and MMP9 [2 Mol Neurobiol] in glioma tissues should be clinically recommended as criteria of glioma grade in department of pathology.