Therapeutic Target For Glioma Research Articles

14-3-3ζ promotes gliomas cells invasion by regulating Snail through the PI3K/AKT signaling.

14‐3‐3ζ has been reported to function as critical regulators of diverse cellular responses. However, the role of 14‐3‐3ζ in gliomas progression remains largely unknown. The expression level of 14‐3‐3ζ and Snail was detected by Western blot analysis and quantitative polymerase chain reaction in different grades of human gliomas. The effect of 14‐3‐3ζ on gliomas progression was measured using cell migration and invasion assay, the colony formation experiment, and CCK‐8 assay. The effect of 14‐3‐3ζ on PI3K/AKT/Snail signaling protein expression levels was tested by Western blotting. Firstly, 14‐3‐3ζ was often up‐regulated in high‐grade gliomas relative to low‐grade gliomas, and this overexpression was significantly related to tumor size, Karnofsky Performance Scale score and weaker disease‐free survival. Secondly, the overexpression of 14‐3‐3ζ promoted gliomas cells proliferation, migration, and invasion. Conversely, the knockdown of 14‐3‐3ζ suppressed gliomas cells proliferation, migration, and invasion. Furthermore, subsequent mechanistic studies showed that 14‐3‐3ζ could activate PI3K/AKT /Snail signaling pathway to facilitate gliomas cells proliferation, migration, and invasion. This study shows that the overexpression of 14‐3‐3ζ can promote remarkably gliomas cells proliferation, migration, and invasion by regulating the Snail protein expression through activating PI3K/AKT signaling, and it may serve as a potential prognostic marker and therapeutic target for gliomas.

MicroRNA-374a Governs Aggressive Cell Behaviors of Glioma by Targeting Prokineticin 2.

MicroRNA-374a has been abnormally expressed in several cancer types; however, its role in glioma remains unclear. Therefore, we aimed to investigate whether microR-374a participated in the progression of glioma. Expression of microR-374a in glioma cell lines and normal cell line was measured by quantitative real-time polymerase chain reaction. Luciferase reporter assay and Western blot were used to detect the targets of microR-374a. In vitro functional experiments were conducted to investigate the biological role of microR-374a. Low expression of microR-374a was found in glioma cell lines. Prokineticin 2 was identified as a direct target of microR-374a in glioma. Investigations on the mechanisms related to glioma progression showed that microR-374a inhibited glioma cell proliferation, cell cycle progression, and cell invasion through targeting Prokineticin 2. Taken together, these results revealed that microR-374a functions as tumor suppressor by targeting Prokineticin 2, suggesting it might be a novel therapeutic target for glioma.

Molecular mechanism of SSFA2 deletion inhibiting cell proliferation and promoting cell apoptosis in glioma

Gliomas are the most common primary brain malignant tumors in humans. Glioblastoma multiforme(GBM) is the most malignant intracranial tumor with a relatively poor prognosis. There promote us to find effective anti-cancer therapies to reduce cancer mortality. By using bioinformatic analysis, we found SSFA2 as a gene with elevated expression in the glioma tissues. We detected the expression of SSFA2 in glioma tissues and in the glioma cell lines, as well as in normal brain tissues. SSFA2 expression was higher in glioma tissues, especially in glioblastoma multiforme than normal brain tissues. Subsequently, we found that down-regulate SSFA2 in glioma cell lines can regulate the cell cycle to reduce the proliferation ability and induce the early apoptosis rate in shSSFA2 cells relative to control cells. Moreover, we found that down-regulate SSFA2 in glioma cell line U87(shSSFA2-U87) inhibited the growth effectiveness compared to the control cell line U87. These result reveals us that SSFA2 may act as oncogene to promote the progression of glioma. For further research specific mechanisms of SSFA2 in gliomas, we used the gene chip to detect the downstream gene in U87. We found that 30 genes also may be as target gene of SSFA2, and we testify the protein expression by western-blot. The result reveal that IL1A, IL1B and CDK6 as target gene of SSFA2 to regulate the progression of glioma. These finding suggest that SSFA2 could be a new therapeutic target for gliomas.

Upregulation of long noncoding RNA MRCCAT1 predicts poor prognosis and functions as an oncogene in glioma.

This study aimed to investigate the expressions, clinical significances, roles, and mechanism of action of MRCCAT1 in glioma. The expression of MRCCAT1 in 103 glioma tissues with different grades and 21 normal brain tissues was measured by qPCR. The prognostic value of MRCCAT1 was investigated by Kaplan-Meier survival analysis. The biological roles of MRCCAT1 on glioma cell proliferation were assessed by Glo cell viability assays and ethynyl deoxyuridine incorporation assays. The roles of MRCCAT1 on glioma cell migration were evaluated by transwell assays. The effects of MRCCAT1 on p38-MAPK signaling were assessed by Western blot. MRCCAT1 is upregulated in glioma tissues and positively associated with glioma grades. Increased expression of MRCCAT1 confers poor prognosis of glioma patients independent of glioma grades. Ectopic expression of MRCCAT1 promotes glioma cell proliferation and migration. Knockdown of MRCCAT1 inhibits glioma cell proliferation and migration. Mechanistically, we found that MRCCAT1 activates p38-MAPK signaling in glioma. MRCCAT1 is upregulated in glioma. Increased expression of MRCCAT1 predicts poor outcome of glioma patients. MRCCAT1 promotes glioma cell proliferation and migration via activating p38-MAPK signaling. MRCCAT1 may be a potential prognostic biomarker and therapeutic target for glioma.

Use of Mendelian Randomization for Identifying Risk Factors for Brain Tumors.

Gliomas are a group of primary brain tumors, the most common and aggressive subtype of which is glioblastoma. Glioblastoma has a median survival of just 15 months after diagnosis. Only previous exposure to ionizing radiation and particular inherited genetic syndromes are accepted risk factors for glioma; the vast majority of cases are thought to occur spontaneously. Previous observational studies have described associations between several risk factors and glioma, but studies are often conflicting and whether these associations reflect true casual relationships is unclear because observational studies may be susceptible to confounding, measurement error and reverse causation. Mendelian randomization (MR) is a form of instrumental variable analysis that can be used to provide supporting evidence for causal relationships between exposures (e.g., risk factors) and outcomes (e.g., disease onset). MR utilizes genetic variants, such as single nucleotide polymorphisms (SNPs), that are robustly associated with an exposure to determine whether there is a causal effect of the exposure on the outcome. MR is less susceptible to confounding, reverse causation and measurement errors as it is based on the random inheritance during conception of genetic variants that can be relatively accurately measured. In previous studies, MR has implicated a genetically predicted increase in telomere length with an increased risk of glioma, and found little evidence that obesity related factors, vitamin D or atopy are causal in glioma risk. In this review, we describe MR and its potential use to discover and validate novel risk factors, mechanistic factors, and therapeutic targets in glioma.

Long noncoding RNA DLX6-AS1 accelerates the glioma carcinogenesis by competing endogenous sponging miR-197-5p to relieve E2F1

Long noncoding RNAs (lncRNAs) participate in numerous of human cancer tumorigenesis. Nevertheless, the in-depth molecular mechanism that lncRNAs regulate the gliomagenesis is still ambiguous. In this research, our study invests energy in the biologic roles of lncRNA DLX6-AS1 on the glioma tumorigenesis. Here, we demonstrated that DLX6-AS1 expression was both high-expressed in the glioma cells and tissue, and the overexpression of DLX6-AS1 was clinically correlated with the poor outcome of glioma patients. In the cellular functional assays, silenced DLX6-AS1 expression by siRNAs inhibited the proliferation, invasion and tumor growth in vitro and in vivo, while the enhanced DLX6-AS1 expression by plasmids promotes them. The bioinformatics predictive tools, luciferase reporter assay and correlation analysis found that miR-197-5p could both target the 3′-UTR of DLX6-AS1 as well as E2F1 gene, constructing DLX6-AS1-miR-197-5p-E2F1 axis. Moreover, receiver operating characteristic (ROC) curve analysis revealed that lncRNA DLX6-AS1 has valuable diagnostic value clinical diagnose for the glioma patients (AUC = 0.736). Overall, our finding supports that DLX6-AS1 accelerates the glioma carcinogenesis by competing endogenous sponging miR-197-5p to relieve E2F1, acting as a novel therapeutic target for glioma.

Long noncoding RNA LINC01426 promotes glioma progression through PI3K/AKT signaling pathway and serves as a prognostic biomarker.

Growing evidence indicated that long intergenic non-protein coding RNA 1426 (LINC01426) played important roles in tumor initiation and progression. However, little was known about the expression pattern and biological function of LINC01426 in glioma. Here, we aimed to determine its expression pattern, clinicopathological significance, and biological roles in glioma. The Cancer Genome Atlas (TCGA) data was used to screen abnormally expressed lncRNAs in glioma. Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was performed to detect the expression of LINC01426 in both glioma tissues and cell lines. Then, the associations between LINC01426 expression levels and various clinicopathologic characteristics and the clinical prognosis of patients with glioma were analyzed. The loss-of-function assay was performed to explore the effect of LINC01426 on glioma proliferation, metastasis, and apoptosis. Western blotting was performed to assess the protein expression levels. We identified a differentially expressed novel oncogenic lncRNA termed as LINC01426 by TCGA. Subsequent RT-PCT indicated that LINC01426 expression was significantly up-regulated in both glioma tissues and cell lines. Increased LINC01426 expression was negatively correlated with WHO grade and KPS score. Furthermore, LINC01426 could serve as an independent predictor for overall survival in glioma. In vitro assay revealed that knockdown of LINC01426 suppressed glioma cells proliferation, migration and invasion, and induced apoptosis. Mechanistic investigation showed that LINC01426 exhibited its tumor promoter role by modulating PI3K/Akt signaling pathway in glioma. The present study indicated that LINC01426 functioned as a tumor promoter and it might be a potential biomarker and therapeutic target in glioma.

CD163, a novel therapeutic target, regulates the proliferation and stemness of glioma cells via casein kinase 2.

Glioma is a devastating cancer with a dismal prognosis and there is an urgent need to discover novel glioma-specific antigens for glioma therapy. Previous studies have identified CD163-positive tumour cells in certain solid tumours, but CD163 expression in glioma remains unknown. In this study, via an analysis of public datasets, we demonstrated that CD163 overexpression in glioma specimens correlated with an unfavourable patient prognosis. CD163 expression was increased in glioma cells, especially primary glioma cells. The loss of CD163 expression inhibited both cell cycle progression and the proliferation of glioblastoma multiforme (GBM) cell lines and primary glioma cells. CD163 interacted directly with casein kinase 2 (CK2) and CD163 silencing reduced AKT/GSK3β/β-catenin/cyclin D1 pathway activity via CK2. Moreover, CD163 was upregulated in CD133-positive glioma stem cells (GSCs), and CD163 downregulation decreased the expression of GSC markers, including CD133, ALDH1A1, NANOG and OCT4. The knockdown of CD163 impaired GSC stemness by inhibiting the CK2/AKT/GSK3β/β-catenin pathway. Finally, a CD163 antibody successfully induced complement-dependent cytotoxicity against glioma cells. Our findings indicate that CD163 contributes to gliomagenesis via CK2 and provides preclinical evidence that CD163 and the CD163 pathway might serve as a therapeutic target for glioma.

LASP1 promotes glioma cell proliferation and migration and is negatively regulated by miR-377-3p

Glioma is one of the most aggressive and lethal human cancers with a low cure rate. LASP1 plays an oncogenic role in multiple human cancers; however, its role in glioma remains largely unknown. Here, we found that LASP1 was highly expressed in glioma tissue samples. Functionally, knockdown of LASP1 significantly suppressed glioma cell proliferation and migration in vitro and tumorigenicity in vivo. These effects were found to be mechanistically associated with suppression of AKT activity. Furthermore, we identified LASP1 as a direct target of miR-377-3p. Overexpression of miR-377-3p reduced the expression of LASP1 and suppressed the proliferation and migration of glioma cells. Restoration of LASP1 expression in miR-377-3p-overexpressing cells attenuated the inhibition of glioma cell malignancy and reversed the dephosphorylation of AKT. Taken together, our results suggest that LASP1 activates the PI3K/AKT signaling pathway and is downregulated by miR-377-3p during glioma progression. These data provide a new possible therapeutic target in glioma.

LGR5, a novel functional glioma stem cell marker, promotes EMT by activating the Wnt/\u03b2-catenin pathway and predicts poor survival of glioma patients

BackgroundTumor recurrence, the chief reason for poor prognosis of glioma, is largely attributed to glioma stem cells (GSCs) and epithelial-mesenchymal transition (EMT). However, the mechanisms among them remain unknown. Here, we determined whether leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), known as a stem cell marker for colon cancer and gastric cancer, can serve as a novel GSC marker involved in EMT and a therapeutic target in glioma.MethodsStemness properties were examined in FACS-isolated LGR5+/LGR5− cells. Reported stem cell markers, EMT and the Wnt/β-catenin pathway were examined in stable LGR5 knockdown or overexpressed GSCs by Western Blot. The treatment experiment was performed in an intracranial orthotopic xenograft model by knockdown of LGR5 or by using the Wnt/β-catenin pathway inhibitor Wnt-C59. LGR5 expression was determined in 268 glioma specimens by immunohistochemistry.ResultsLGR5+ cells possessed stronger stemness properties compared to LGR5− cells. The expression of SOX2, Nanog, CD133, CD44, CD24 and EpCAM was modulated by LGR5. Both LGR5 knockdown and Wnt-C59 reduced tumor invasion and migration and blocked EMT by inhibiting the Wnt/β-catenin pathway in vitro and suppressed the intracranial orthotopic xenograft growth and prolonged the survival of xenograft mice in vivo. Moreover, LGR5 was positively correlated with Ki67, N-cadherin and WHO grade and negatively correlated with IDH1. Glioma patients with high expression of LGR5 showed significantly poorer prognosis.ConclusionsLGR5 is a new functional GSC marker and prognostic indicator that can promote EMT by activating the Wnt/β-catenin pathway and would thus be a novel therapeutic target for glioma.

LncRNA SNHG3 enhances the malignant progress of glioma through silencing KLF2 and p21.

As a newly discovered long non-coding RNA, small nucleolar RNA host gene 3 (SHNG3) has been reported to be dysregulated in certain cancers. Nevertheless, the details about clinical values and biological effects of SNHG3 on glioma are still covered. In this paper, we determined the expression level of SNHG3 in glioma tissues and cells and evaluated the effect of SNHG3 expression on the prognosis of glioma patients. The functional assays were applied to define the effects of SNHG3 on the biological behaviors in glioma including cell proliferation, cell cycle, and apoptosis. It was revealed that SNHG3 was much more enriched in glioma tissues and cell lines than in normal ones. Furthermore, gain- or loss-of-function experiments indicated that the up-regulation of SNHG3 promoted cell proliferation, accelerate cell cycle progress, and repressed cell apoptosis. The mechanistic assays disclosed that SNHG3 facilitated the malignant progression of glioma through epigenetically repressing KLF2 and p21 via recruiting enhancer of zeste homolog 2 to the promoter of KLF2 and p21. Generally, it was exposed that SNHG3 might function as an oncogene in glioma and could be explored as a potential prognostic biomarker and therapeutic target for glioma.

Novel lncRNA-ZNF281 regulates cell growth, stemness and invasion of glioma stem-like U251s cells.

Glioma is the most common sub-type of brain tumor. Due to the presence of stem-like cells, it is characterized by poor prognosis, aggressive ability and high post-surgical recurrence rates. Hence, there is critical need to identify molecular mechanisms of glioma stem-like cells. We found a novel lncRNA in the ZNF281 gene and named it lncRNA-ZNF281. We detected the expression of lncRNA-ZNF281 in glioma stem-like cells (U251s), the glioma cell line (U251) and also in normal brain tissue. The expression of lncRNA-ZNF281 was lower in glioma stem-like cells (U251s) and this indicates that lncRNA-ZNF281 can regulate the self-renewal capacity of glioma stem-like cells and stem cell marker expression. Most significantly, lncRNA-ZNF281 inhibits the invasion of glioma stem-like cells by regulating the expression of the NF-κB1 signaling pathway. Our data demonstrates that lncRNA-ZNF281 inhibits the self-renewing ability and invasion of GSCs in vitro and in vivo and can reduce tumorigenicity in the glioma stem-like cell (U251s). The underlying mechanisms may involve the regulation of stem cell markers (CD133, Nestin, OCT4 and Nanog) to reduce the self-renewal ability and regulate the NF-κB1 signaling pathway and inhibit U251s glioma stem-like cell invasion. These finding suggest that lncRNA-ZNF281 could be a successful new therapeutic target in glioma.

LncRNA GHET1 down-regulation suppresses the cell activities of glioma.

Long noncoding RNAs (lncRNAs) are emerging as new modulators in cancer origination and progression. The previous study found lncRNA gastric carcinoma highly expressed transcript 1 (GHET1) was significantly up-regulation in the gastric cancer. In our present study, we studied the GHET1 expression in glioma and its effects to biological activities of glioma in vitro and vivo studies. In the clinical analysis, the results were shown that lncRNA GHET1 was significantly up-regulation and the Numb protein expression was significantly down-regulation in glioma tissues. In vitro and vivo studies, the results were shown that lncRNA GHET1 knock-down had effects to inhibit biological activities by regulation Numb and down-stream genes P53 and MMP2/9. The results suggested that GHET1 is a novel tumor oncogene by Numb in glioma. LncRNA GHET1 may serve as a potential biomarker and therapeutic target for glioma.

Fatal correlation between YAP1 expression and glioma aggressiveness: clinical and molecular evidence.

During the last decade, large-scale genomic analyses have clarified the somatic alterations in gliomas, providing new molecular classification based on IDH1/2 mutations and 1p19q codeletion with more accurate patient prognostication. The Hippo pathway downstream effectors, YAP1 and TAZ, have recently emerged as major determinants of malignancy by inducing proliferation, chemoresistance, and metastasis in solid tumors. In this study, we investigated the expression of YAP1 in 117 clinical samples of glioma described according to the WHO 2016 classification. We showed for the first time that YAP1 was tightly associated with glioma molecular subtypes and patient outcome. We validated our results in an independent cohort from the TCGA database. More interestingly, we found that YAP1 may have prognostic significance for predicting patient survival, especially in low-grade gliomas. Using patient-derived glioblastoma stem cell cultures, we demonstrated that YAP1 was activated and that it controlled cell proliferation. Transcriptome analysis revealed lower expression of YAP1 in the proneural GBM subtype. Furthermore, we found that overexpression of YAP1 was sufficient to inhibit the OLIG2 proneural marker, suggesting its involvement in maintenance of the GBM phenotype. Taken together, our results showed that YAP1 could be a relevant prognostic biomarker and a potential therapeutic target in glioma. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

MiR-363-3p modulates cell growth and invasion in glioma by directly targeting pyruvate dehydrogenase B.

This study is designed to investigate the role of miR-363-3p in the cancer development of glioma. The expression of miR-363-3p in glioma and adjacent noncancerous tissue was measured using quantitative RT-PCR. The expression of a target gene of miR-363-3p, pyruvate dehydrogenase B (PDHB), was determined by Western blot. The level of miR-363-3p was increased or decreased by transfected with miR-363-3p mimic or miR-363-3p inhibitor, respectively. The impact of miR-363-3p on cell growth, apoptosis and invasion was determined by CCK-8 (Cell Counting Kit) assay, flow cytometry, and transwell assay. The role of PDHB in mediating the oncogenic activities was demonstrated by co-transfected PDHB vector and miR-363-3p mimic. Our results have shown that miR-3663-3p level was significantly higher in glioma tissue. Furthermore, miR-363-3p functions as onco-miRNA, promotes cell proliferation, protects against apoptosis, and enhances invasion by directly targeting PDHB. MiR-363-3p is an onco-miRNA, which can be considered as a potential therapeutic target in glioma.

Long non-coding RNA SNHG12promotes the proliferation and migration of glioma cells by binding to HuR.

Long non-coding RNAs (lncRNAs) play important roles in biological processes and provide a novel approach with which to understand the molecular mechanisms responsible for glioma. Previous studies have demonstrated that lncRNA small nucleolar RNA host gene12 (SNHG12) is involved in cell growth and migration. However, the accurate expression pattern of SNHG12 in glioma and the possible associations between this pattern and the clinicopathological characteristics of glioma cohorts are not yet known. The present study investigated the role of lncRNA SNHG12 in the development and progression of glioma, as well as the potential diagnostic value of SNHG12 in patients with glioma. The levels of SNHG12 were detected in resected specimens from patients and in glioma cell lines using reverse transcription-quantitative polymerase chain reaction. The potential effects of SNHG12 on the viability, mobility and apoptosis of glioma cells were evaluated using invitro assays. The association between SNHG12 and Hu antigenR(HuR) was also determined using RNA immunoprecipitation (RIP) and RNA pull-down assays. The results revealed that SNHG12 was significantly upregulated in glioma tissues and cell lines. High levels of SNHG12 were associated with the deterioration of patients with glioma. Patients with high levels of SNHG12 exhibited a reduced 5-year overall survival rate (compared to those with lower levels), particularly in cohorts with high-grade carcinoma(III-IV). The silencing of SNHG12 expression by RNA interference led to a reduced viability and mobility, and in an increased apoptosis of human glioma cells. Furthermore, RIP and RNA pull-down assays demonstrated that SNHG12 was associated with and was stabilized by HuR. The findings of the present study thus identify a novel therapeutic target in glioma.

ARL2 overexpression inhibits glioma proliferation and tumorigenicity via down-regulating AXL

BackgroundGlioma is the most common primary brain tumor in adults with a poor prognosis. As a member of ARF subfamily GTPase, ARL2 plays a key role in regulating the dynamics of microtubules and mitochondrial functions. Recently, ARL2 has been identified as a prognostic and therapeutic target in a variety range of malignant tumors. However, the biological functional role of ARL2 in glioma still remains unknown. The aim of this study was to explore the expression and functional role of ARL2 in glioma.MethodsIn this study, we investigated the expression of ARL2 in glioma samples by using RT-PCR, immunohistochemistry and western blot. The correlation between ARL2 expression and the outcomes of glioma patients was evaluated with survival data from TCGA, CGGA and Rembrandt dataset. Lentiviral technique was used for ARL2 overexpression in U87 and U251 cells. CCK8 assay, colony formation assay, wound healing test, transwell invasion assay and in vivo subcutaneous xenograft model were performed to investigated the biological functions of ARL2.ResultsARL2 expression was down-regulated in glioma, and was inversely associated with poor prognosis in glioma patients. Furthermore, exogenous ARL2 overexpression attenuated the growth and colony-formation abilities of glioma cells, as well as their migration and invasive capabilities. Moreover, elevated expression of ARL2 inhibited in vivo tumorigenicity of glioma cells. Mechanistically, ARL2 regulated AXL expression, which was known as an important functional regulator of proliferation and tumorigenicity in glioma cells.ConclusionOur study suggests that ARL2 inhibits the proliferation, migration and tumorigenicity of glioma cells by regulating the expression of AXL and may conduct as a new prognostic and therapeutic target for glioma.

Overexpression of STAT1 suppresses angiogenesis under hypoxia by regulating VEGF‑A in human glioma cells

Hypoxia is common in Glioblastoma (GBM). By regulating the ‘hypoxia signaling cascade’, hypoxia affects several processes including cell proliferation, invasion, and angiogenesis. Some studies have revealed that signal transducer and activator of transcription (STAT), including STAT1, is abnormal under hypoxia in several cancers. Here, we investigated the role of STAT1 under hypoxia in glioma progression. We found that STAT1 was downregulated under a hypoxic condition in U251 and U373. STAT1 overexpression can not only decrease proliferation, migration and invasion in U251 and U373 but also inhibit tube formation of HBMECs. Moreover, overexpression of STAT1 decreased tumor growth and prolonged the overall survival of xenograft mice. We also showed that STAT1 overexpression inhibited the expression of HIF-1α and VEGF-A. Our work suggests that STAT1 plays a pivotal role as a tumor suppressor in glioma under hypoxia, and it could be a potential new therapeutic target in glioma.

HOXC10 promotes proliferation and invasion and induces immunosuppressive gene expression in glioma.

The prognosis for patients with malignant glioma is very poor and thus the identification of new potential therapeutic targets is critically important. In this work, we report a previously unknown role for the homeobox transcription factor HOXC10 in regulating immunosuppressive gene expression in glioma cell lines and their proliferative and invasive capacities. Although HOXC10 expression is dysregulated in several types of tumors, its potential function in glioma was not known. We found that HOXC10 expression was upregulated in glioma compared with normal tissue, and that HOXC10 expression positively associated with high grading of glioma. In three independent datasets (REMBRANDT glioma, The Cancer Genome Atlas glioblastoma multiforme and GSE4412), HOXC10 upregulation was associated with short overall survival. In two glioma cell lines, HOXC10 knock-down inhibited cell proliferation, colony formation, migration and invasion, and promoted apoptosis. In addition, HOXC10 knock-down suppressed the expression of genes that are involved in tumor immunosuppression, including those for transforming growth factor-β 2, PD-L2, CCL2 and TDO2. A ChIP assay showed that HOXC10 directly bound to the PD-L2 and TDO2 promoter regions. In summary, our results suggest that HOXC10 upregulation in glioma promotes an aggressive phenotype and induces immunosuppressive gene expression, supporting further investigation of the potential of HOXC10 as a therapeutic target in glioma.

Knockdown of PLK1 inhibits invasion and promotes apoptosis in glioma cells through regulating autophagy.

Polo like kinase 1 (PLK1), an oncogene, is a ubiquitously expressed serine/threonine protein kinase. We aimed at investigating the role of PLK1 in glioma. Clinical glioma specimens were obtained from Zhejiang Hospital (Hangzhou, Zhejiang, China). The mRNA and protein levels of PLK1 in glioma tissues and different glioma cells were analyzed by Real-time PCR and Western blot, respectively. The expression of PLK1 protein in glioma tissues was also determined by immunohistochemistry staining. Then, the effect of PLK1 on cell proliferation and apoptosis of U251 and U87 cells was analyzed by using CCK-8 assay and Annexin V/PI staining, respectively. Furthermore, the migration and invasion of glioma cells were examined by transwell assay. Finally, the protein levels of autophagy indicators LC3-II, ATG5 and p-p70 S6 in U251 and U87 cells were detected by Western blot, and the expression of E-cadherin, vimentin and MMP9 and apoptosis associated indicators Bax, cleaved caspase-3 and Bcl-2 in U251 cells were also determined using Western blot. PLK1 was upregulated in glioma tissues and cells. Knockdown of PLK1 significantly inhibited cell proliferation, migration, invasion, and induced apoptosis of U87 and U251 glioma cells. Furthermore, the data demonstrated that knockdown of PLK1 significantly elevated expression of cleaved caspase-3, BIM, BAX, and E-cadherin, and reduced expression of MMP9, ATG5 and LC3-II in U251 and U87 cells. Additionally, we found that knockdown of PLK1 can inhibit autophagy in glioma cells. Knockdown of PLK1 can inhibit the glioma development by suppressing the autophagy and enhancing the apoptosis of glioma cells. PLK1 may be a potential therapeutic target in gliomas.