Promotes Glioma Cell Proliferation Research Articles

A positive feedback loop of miR-30a-5p-WWP1-NF-κB in the regulation of glioma development.

Previous studies demonstrated that miR-30a-5p promotes glioma cell growth and invasion. Furthermore, WWP1 (WW domain containing E3 ubiquitin protein ligase 1) inhibits NF-κB activation that is strongly correlated with gliomagenesis. Using the GEO database and bioinformatics analyses, we identified WWP1 was downregulated in glioma tissues and might be a putative target for miR-30a-5p. Hence, this study aims to explore the interaction among miR-30a-5p, WWP1, and NF-κB and their roles in the regulation of glioma development. We found decreased WWP and increased miR-30a-5p expression and p65 phosphorylation in glioma tissues. Furthermore, WWP1 mRNA level was negatively correlated with miR-30a-5p expression in glioma tissues. Interestingly, miR-30a-5p targeted WWP1 expression. Additionally, NF-κB p65 overexpression increased miR-30a-5p expression through direct binding of NF-κB RelA subunit to the promoter of miR-30a-5p. We also confirmed that WWP1 overexpression decreased phosphorylation of NF-κB p65. Importantly, miR-30a-5p promoted glioma cell proliferation, migration, and invasion via targeting WWP1. Furthermore, NF-κB p65 overexpression inhibited WWP1 expression and promoted glioma cell malignant behaviors via inducing miR-30a-5p transcription. Moreover, WWP1 overexpression decreased miR-30a-5p expression and inhibited glioma cell malignant behaviors via inhibiting NF-κB p65. Our further assay showed that WWP1 inhibited in vivo growth of xenograft tumors of glioma cells, accompanied with a decrease in miR-30-5p expression and phosphorylation of NF-κB p65. In conclusion, there is a "miR-30a-5p-WWP1-NF-κB" positive feedback loop, which plays an important role in regulating glioma development and might provide a potential therapeutic strategy for treating glioma.

Long non-coding RNA BLACAT1 promotes the proliferation and invasion of glioma cells via Wnt/β-catenin signaling.

Long non-coding RNAs (lncRNAs) are hypothesized to regulate numerous biological behaviors in human cancers. The present study aimed to explore the roles of lncRNA bladder cancer associated transcript 1 (BLACAT1) in glioma. The expression of BLACAT1 in glioma tissues and cell lines was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). CCK-8 assay, colony formation assay, wound healing assay and Transwell invasion assay were used to explore the roles of BLACAT1 in glioma cells. RT-qPCR and western blot analysis were used to determine the BLACAT1 molecular mechanism. The findings demonstrated that lncRNA BLACAT1 was overexpressed in glioma tissues and cell lines. High BLACAT1 expression was correlated with high tumor grade in glioma patients. Functional assays determined that BLACAT1 promoted glioma cell proliferation, migration, invasion and epithelial-mesenchymal transition in vitro. In addition, it was demonstrated that BLACAT1 activated the Wnt/β-catenin signaling pathway. In conclusion, BLACAT1 may serve as an oncogenic lncRNA in glioma progression via activation of the Wnt/β-catenin signaling pathway. Therefore, BLACAT1 may be a novel therapeutic target for glioma treatment.

LKB1 suppresses glioma cell invasion via NF-κB/Snail signaling repression.

BackgroundLiver kinase B1 (LKB1) is involved in various human diseases. Aberrant expression of LKB1 expression is involved in glioma progression and associated with prognosis, however, the specific mechanism involving NF-κB/Snail signaling pathways remain unknown.Materials and methodsIn the present study, quantitative real-time PCR analysis was used to investigate the expression of LKB1 tumor tissue samples and cell lines. In glioma cell lines, CCK-8 assay, transwell invasion and migration assays were used to investigate the effects of LKB1on proliferation and invasion.ResultsWe observed that LKB1 knockdown promoted glioma cell proliferation, migration and invasion. This effect was induced through NF-κB/Snail signaling activation. Also, LKB1 overexpression suppressed proliferation, migration, and invasion, which could be rescued by Snail overexpression.ConclusionTaken together, our results show that LKB1 knockdown promotes remarkably glioma cell proliferation, migration and invasion by regulating Snail protein expression through activating the NF-κB signaling. This may serve as a potential prognostic marker and therapeutic target for glioma.

The expression and clinical significance of Rho-associated Kinase 1 in glioma tissues

Objective To explore the expression and significance of Rho-associated kinase 1 (ROCK1) in glioma. Methods Western blotting was used to detect the protein expression levels of ROCK1 in glioma tissues. Product-Limit (Kaplan-Meier) was used to analyze the relationship between ROCK1 and clinical features of glioma patients. Small interfering RNA (siRNA) interference was applied to inhibit the expression of ROCK1 in glioblastoma cells. The migration of U251 cells was measured by Transwell assay. The proliferation of U251 cells was examined by cell counting kit-8 (CCK-8) assay. Results Western blotting results showed that ROCK1 protein was highly expressed in glioma tissues. The expression of ROCK1 was not significantly correlated with gender, age, and tumor size (P>0.05), but significantly with World health organization (WHO) classification (P<0.05). Kaplan-Meier analysis showed that the median of ROCK1 high expression group was 13.00±2.04, and that of ROCK1 low expression group was 25.00±6.98. Patients with high expression of ROCK1 had a poor prognosis (P<0.01). Transwell assay results showed that there was a 45%-50% reduction in number of transmembrane cells in si-ROCK1 group, indicating that ROCK1 promotes cancer cell invasion. Transwell migration assay results showed the number of transmembrane cells in the si-ROCK1 group was reduced by 45%-50%, indicating that ROCK1 promotes tumor cell invasion. CCK-8 assay results showed that the number of clonal cells in the si-ROCK1 group was reduced by about 56 compared to the control group, indicating that ROCK1 promotes glioma cell proliferation. Conclusion ROCK1 is highly expressed in glioma patients and is associated with the development, progression, and metastasis of glioma. Key words: Rho-associated protein kinase 1; Glioma; Invasion; Proliferation

TRIM31 promotes glioma proliferation and invasion through activating NF-κB pathway.

BackgroundGlioma is the most lethal primary brain tumor, the survival rate still isn’t improved in the past decades. It’s essential to study the regulatory mechanism of glioma progression, hoping to find new therapy targets or methods. The family of tripartite motif (TRIM) containing proteins are E3 ubiquitination ligases, which play critical role in various tumor progression.MethodsCell proliferation and invasion were analyzed by colony formation assay, soft agar growth assay, BrdU incorporation assay and transwell invasion assay. Luciferase reporter analysis was used to analyze NF-κB pathway activity.ResultsWe found TRIM31 was upregulated in glioma cells and tissues, its overexpression significantly promoted glioma cell proliferation and invasion, while its knockdown significantly inhibited glioma cell proliferation and invasion. Mechanism analysis found TRIM31 promoted NF-κB pathway activity and increased its targets expression. NF-κB inhibition reversed the phenotype caused by TRIM31, confirming TRIM31 promoted glioma progression through activating NF-κB pathway. Using clinical specimens found TRIM31 expression was positively correlative with NF-κB activity.ConclusionThis study found TRIM31 promoted glioma proliferation and invasion through activating NF-κB activity.

Downregulation of KLF13 through DNMT1-mediated hypermethylation promotes glioma cell proliferation and invasion.

BackgroundRecent evidence indicates that Kruppel-like factor 13 (KLF13) has critical roles in regulating cell differentiation, proliferation and may function as a tumor suppressor. However, its role in glioma progression is poorly understood.MethodsPublic database was used to explore the expression and prognostic value of KLF13 in glioma. Cell proliferation and invasion assays were used to explore the role of KLF13. Bisulfite sequencing and ChIP assay were used to determine the methylation of KLF13 promoter in glioma and the regulation of KLF13 by DNMT1.ResultsWe found that KLF13 inhibited glioma cell proliferation and invasion, which could be reversed by AKT activation. DNMT1-mediated hypermethylation was responsible for downregulation of KLF13. Knocking down of DNMT1 restored KFL13 expression and inhibited cell proliferation and invasion as well. Patients with high expression of KLF13 might have a better prognosis.ConclusionKLF13 suppressed glioma aggressiveness and the regulation of KLF13 could be a potential therapeutic target.

Long non-coding RNA AGAP2-AS1 promotes the proliferation of glioma cells by sponging miR-15a/b-5p to upregulate the expression of HDGF and activating Wnt/β-catenin signaling pathway.

Glioma is a kind of malignant brain tumor which damages the central nervous system of adults. Recent years, the molecular mechanism involved in the initiation and progression of glioma has been widely reported. Long non-coding RNAs (lncRNAs) have been proved to be significant modulators in the biological processes of glioma. In this study, we found that lncRNA AGAP2-AS1 was differentially expressed in glioma tissue samples and cell lines. Kaplan-Meier method was used to analyze the correlation between AGAP2-AS1 expression and the overall survival of glioma patients. Higher expression of AGAP2-AS1 was correlated with the lower overall survival of glioma patients. Functionally, AGAP2-AS1 knockdown inhibited glioma cell proliferation and accelerated glioma cell apoptosis. Mechanistically, AGAP2-AS1 upregulated HDGF by sponging miR-15a/b-5p. The function of AGAP2-AS1-miR-15a/b-5p-HDGF axis was confirmed by performing rescue assays. Experimental results suggested that miR-15a/b-5p and HDGF involved in AGAP2-AS1-mediated glioma cell proliferation. Moreover, AGAP2-AS1 and HDGF were found to activate Wnt/β-catenin signaling pathway in glioma cell lines. In summary, this study demonstrated that AGAP2-AS1 promoted glioma cell proliferation by sponging miR-15a/b-5p to upregulate the expression of HDGF.

The expression and clinical significance of forkhead box protein K1 in glioma tissues

Objective Explore of the expression and significance of forkhead box protein K1 (FOXK1) in glioma. Methods Real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) and Western blotting analysis of mRNA and protein expression levels of FOXK1 in glioma tissues; Kaplan-Meier analysis of the relationship between FOXK1 and prognosis parameters; RNA interference on the expression of FOXK1 in glioblastoma cell. Transwell migration assay for the migration of LN18 cells. Cell counting kit-8 (CCK-8) counting for T98G cell proliferation. Results RT-qPCR and Western blotting showed that FOXK1 mRNA and protein is highly expressed in glioma tissues. The expression of FOXK1 was not significantly correlated with gender (P>0.05) and age of glioma patients (P>0.05), while FOXK1 expression was significantly with WHO classification (P<0.01). Kaplan-Meier analysis found that patients with high expression of FOXK1 had a poor prognosis (P<0.05). Transwell migration assay results indicate that FOXO1 promotes cancer cell metastasis. The CCK-8 cell count results indicate that FOXK1 promotes glioma cell proliferation. Conclusion FOXK1 is highly expressed in glioma patients and is associated with glioma development, progression, and metastasis. Key words: Forkhead box protein K1; Glioblastoma; Metastasis

ECT2/PSMD14/PTTG1 axis promotes the proliferation of glioma through stabilizing E2F1.

Epithelial cell transformation sequence 2 (ECT2) is upregulated in glioma and promotes glioma cell proliferation. A preliminary experiment showed a positive correlation between ECT2 and pituitary tumor-transforming gene 1 (PTTG1). The aim of this study was to explore how ECT2 affects PTTG1 to influence the proliferation of glioma cells. The expression of ECT2 in glioma was detected by western blot and reverse transcription PCR. The effect of ECT2 on glioma proliferation was examined using cell proliferation-related assays and in vivo experiments. The effect of ECT2 on the stability of E2F transcription factor 1 (E2F1) and the expression of PTTG1 were examined by western blot, co-immunoprecipitation, and in vivo ubiquitination assays. ECT2 was upregulated in gliomas and was negatively correlated with prognosis; its downregulation inhibited glioma cell proliferation. Furthermore, ECT2 regulated PTTG1 expression by affecting the stability of E2F1, thereby affecting the glioma cell proliferation. In addition, the deubiquitinating enzyme proteasome 26S subunit, non-ATPase 14 (PSMD14) affected the degradation of E2F1 and regulated the stability of E2F1. Interestingly, ECT2 regulated the expression of PSMD14. In this study, we clarify a new mechanism by which ECT2 regulates the expression of PTTG1 and thus affects the proliferation of glioma cells: ECT2 influences the stability of E2F1 by regulating the expression of the deubiquitinating enzyme PSMD14, thereby affecting the expression of PTTG1. Intensive and extensive understanding of the mechanism of ECT2 in glioma proliferation may provide an opportunity for the development of new molecular therapeutic targets for glioma treatment.

Long non‑coding RNA PVT1 promotes glioma cell proliferation and invasion by targeting miR‑200a

Glioma is a type of malignant tumor accounting for 80% of all brain cancer morbidity. The long non-coding RNA (lncRNA) PVT1 has been demonstrated to be an oncogenic lncRNA in other types of cancer. However, the role of PVT1 in glioma is still unknown. The aim of the present study was to investigate the role of PVT1 in glioma, and its potential association with microRNA (miR)-200a. miR-200a mimics and small interfering (si)RNA transfection were utilized to construct miR-200a overexpression and knockdown models to investigate the effect of miR-200a on glioma cells. Slow-virus infection was used to transfect cells. Western blotting and reverse transcription-quantitative polymerase chain reaction were applied for the quantitative analysis of mRNA and protein expression. Apoptosis of podocytes was detected by terminal deoxynucleotidyl-transferase-mediated dUTP nick end labelling staining. PVT1 expression in glioma was upregulated. In vitro, PVT1 silencing via transfection with si-PVT1 suppressed proliferation and invasion and induced G0/G1 phase arrest. Luciferase reporter assay revealed the association between miR-200a and the PVT1 3'-untranslated region. Furthermore, experiments examining both miR-200a and PVT1 indicated that miR-200a could reverse the effects of PVT1 on glioma cell phenotypes. The present study reveals the overexpression of PVT1 in glioma tissue and cells and the oncogenic role of PVT1 in gliomagenesis via sponging miR-200a, thus providing a potential biomarker for the early detection of glioma and prognosis prediction.

Expression and clinical significance of vaccinia virus-associated kinase 1 in glioma tissues

Objective To explore the expression and significance of vaccinia virus-associated kinase 1 (VRK1) in glioma. Methods Western blotting was used to detect the protein expression levels of VRK1 in glioma tissues. Kaplan-Meier was applied to analyze the relationship between VRK1 and prognosis parameters. The expression of VRK1 in glioma cells RNA interference on. Cell counting kit-8 (CCK-8) cell counts and colonies for analysis of cell proliferation. Results Western blotting showed that VRK1 protein is highly expressed in glioma tissues. The expression of VRK1 was not significantly correlated with gender and age of glioma patients (P=0.556), while VRK1 expression was significantly with WHO classification (P=0.002). Kaplan-Meier analysis found that patients with high expression of VRK1 had a poor prognosis (P=0.050). The CCK-8 cell count and colony results indicate that VRK1 promotes glioma cell proliferation. Conclusion The high expression of VRK1 in glioma patients is related to the development of glioma. Key words: Vaccinia virus-related kinase 1; Glioma; Survival analysis

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.

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.

Prosaposin promotes the proliferation and tumorigenesis of glioma through toll-like receptor 4 (TLR4)-mediated NF-κB signaling pathway.

BackgroundAs a neurotrophic factor, prosaposin (PSAP) can exert neuroprotective and neurotrophic effects. It is involved in the occurrence and development of prostate and breast cancer. However, there is no research about the role of PSAP in glioma.MethodsThe PSAP overexpressed or silenced glioma cells or glioma stem cells were established based on Lentiviral vector transfection. Cell viability assay, Edu assay, neurosphere formation assay and xenograft experiments were used to detect the proliferative ability. Western blot, Elisa and luciferase reporter assays were used to detect the possible mechanism.FindingsOur study firstly found that PSAP was highly expressed and secreted in clinical glioma specimens, glioma stem cells, and glioma cell lines. It was associated with poor prognosis. We found that PSAP significantly promoted the proliferation of glioma stem cells and cell lines. Moreover, PSAP promoted tumorigenesis in subcutaneous and orthotopic models of this disease. Furthermore, GSEA and KEGG analysis predicted that PSAP acts through the TLR4 and NF-κB signaling pathways, which was confirmed by western blot, immunoprecipitation, immunofluorescence, and use of the TLR4-specific inhibitor TAK-242.InterpretationThe findings of this study suggest that PSAP can promote glioma cell proliferation via the TLR4/NF-κB signaling pathway and may be an important target for glioma treatment.FundThis work was funded by National Natural Science Foundation of China (Nos. 81101917, 81270036, 81201802, 81673025), Program for Liaoning Excellent Talents in University (No. LR2014023), and Liaoning Province Natural Science Foundation (Nos. 20170541022, 20172250290). The funders did not play a role in manuscript design, data collection, data analysis, interpretation nor writing of the manuscript.

Oncogenic DIRAS3 promotes malignant phenotypes of glioma by activating EGFR-AKT signaling

Epidermal growth factor receptor (EGFR)-Akt signaling cascade activation plays a pivotal role in gliomas malignant phenotype, especially in Classical and Mesenchymal subtype gliomas. However, the molecules and mechanisms underlying regulate and maintain the activation of EGFR-AKT signaling remains unclear. Previously reports showed that DIRAS3 inhibits cell proliferation and induces autophagy in ovarian, breast, lung and prostate cancers, which is heterozygosity loss or down-regulated in aforementioned cancers and functionally as a tumor suppressor, whereas the role of DIRAS3 in glioma is still veiled. Here, in this study, we investigated the biological function and role of DIRAS3 in gliomas, and found that DIRAS3 is up-regulated in gliomas and is positively correlated with poor prognosis of glioma patients, meanwhile, over-expressed DIRAS3 promotes glioma cells proliferation and invasion. Further mechanistic study showed that the expression level of DIRAS3 in Classical and Mesenchymal subtype GBMs is higher, and over-expression of DIRAS3 promotes EGFR-AKT signaling activation at the downstream of EGFR and increases AKT phosphorylation, meanwhile suppression of AKT by MK-2206 reverses the tumor promoting function of DIRAS3. Taken together, these findings reveal a novel oncogenic role of DIRAS3 in the development and progression of glioma, which suggest that DIRAS3 could serve as a potential diagnostic marker and a promising therapeutic target of gliomas.

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.

Histone deacetylase HDAC4 promotes the proliferation and invasion of glioma cells.

Glioma is the most lethal type of primary brain tumor characterized by aggressiveness and a poor prognosis. Histone deacetylase4 (HDAC4) is frequently dysregulated in human malignancies. However, its biological functions in the development of glioma are not fully understood. The present study aimed to evaluate HDAC4 expression in human glioma and to elucidate the mechanistic role of HDAC4 in glioma. The results suggested that HDAC4 was significantly upregulated in glioma tissues and a number of glioma cell lines compared with adjacent non-tumor tissues and the non-cancerous human glial cell line SVG p12, respectively (P<0.05). The proliferation, adenosine triphosphate (ATP) levels and invasion ability were substantially enhanced in U251 cells with HDAC4 overexpression, and suppressed in U251 cells with a knockdown of HDAC4 compared with that in U251 cells transfected with the negative control. Knockdown of HDAC4 resulted in cell cycle arrest at the G0/G1 phase and induced the increase of reactive oxygen species level in U251 cells. Furthermore, HDAC4 overexpression was revealed to substantially inhibit the expression of cyclin-dependent kinase (CDK) inhibitors p21 and p27, and the expression of E-cadherin and β‑catenin in glioma U251 cells. Knockdown of HDAC4 substantially promoted the expression of CDK1 and CDK2 and vimentin in glioma U251 cells. Mechanistically, the results of the present study demonstrated that HDAC4 displayed a significant upregulation in glioma, and promoted glioma cell proliferation and invasion mediated through the repression of p21, p27, E-cadherin and β‑catenin, and the potentiation of CDK1, CDK2 and vimentin. Altogether, the present study revealed that HDAC4 overexpression was central for the tumorigenesis of glioma, which may serve as a useful prognostic biomarker and potential therapeutic target for glioma.

Long non‑coding RNA ferritin heavy polypeptide 1 pseudogene3 controls glioma cell proliferation and apoptosis via regulation of the microRNA‑224‑5p/tumor protein D52 axis.

The aim of the present study was to investigate the potential role and regulatory mechanism of long non-coding RNA ferritin heavy polypeptide 1 pseudogene 3 (FTH1P3) in glioma development. The expression of FTH1P3 in low- and high-grade glioma tissues was investigated using reverse transcription-quantitative polymerase chain reaction. FTH1P3 expression was overexpressed or suppressed in U251 glioma cells to examine the involvement of FTH1P3 in glioma cell proliferation and apoptosis using MTT assay and flow cytometry respectively. In addition, the regulatory association between FTH1P3, microRNA (miR)-224-5p and tumor protein (TP) D52 was investigated to elucidate the potential underlying mechanisms of FTH1P3 in glioma by luciferase reporter assay. The results revealed that FTH1P3 was up-regulated in glioma tissues, and FTH1P3 expression in high-grade glioma tissues was significantly higher compared with that in low-grade glioma tissues. Upregulation of FTH1P3 promoted glioma cell proliferation and inhibited apoptosis. Furthermore, FTH1P3 inhibited miR-224-5p expression, which in turn negatively regulated TPD52 expression. Overexpression of miR-224-5p significantly inhibited U251 cell proliferation and induced cellular apoptosis; this effect was clearly reversed following co-transfection of miR-224-5p and TPD52. These data revealed that upregulation of FTH1P3 may have promoted glioma cell proliferation and inhibited apoptosis. Thus, the miR-224-5p/TPD52 axis may be a downstream mechanism of FTH1P3 in glioma progression. The findings of the present study may provide a theoretical basis for the study of the treatment of glioma in the future.

CircRNA circHIPK3 serves as a prognostic marker to promote glioma progression by regulating miR-654/IGF2BP3 signaling

Emerging evidences show RNA back-splicing produces a new type of noncoding RNA, namely circular RNA (circRNA). Many reports demonstrate that circRNA circHIPK3 exerts oncogenic or anti-tumor roles in different cancers, such as ovarian cancer, bladder cancer, osteosarcoma, colorectal cancer and liver cancer. However, no study about circHIPK3 function in glioma exists until today. In this study, we showed that circHIPK3 was upregulated in glioma tissues. Elevated level of circHIPK3 was linked to poor prognosis. Functional investigation indicated that circHIPK3 promotes glioma cell proliferation and invasion, and tumor propagation in vivo. Furthermore, miR-654 was identified as a target of circHIPK3 while IGF2BP3 was targeted by miR-654. CircHIPK3 could promote IGF2BP3 expression via interacting with miR-654 in glioma cells. Finally, CCK8 and transwell assays illustrated that IGF2BP3 overexpression could reverse the effects of IGF2BP3 depletion. Altogether, our findings demonstrated that circHIPK3 contributes to glioma progression through targeting miR-654 from IGF2BP3 and implies circHIPK3 might be a potential target for glioma therapy.

Repression of Dok7 expression mediated by DNMT1 promotes glioma cells proliferation

Malignant glioma is one of the most common primary human tumors in the central nervous system. The molecular mechanisms of the progression and development of glioma have been largely unexplored. In this study, we illustrated that the expression of Dok7 was downregulation in human glioma tissues. Dok7 overexpression significantly inhibits proliferation and colony formation in vitro, and the xenograft tumor formation in vivo. In addition, 5-Aza-2′-deoxycytidine (5-Aza), a DNA methylation inhibitor, preventing the loss of Dok7 expression by decreasing aberrant hypermethylation of Dok7 promoter in glioma cells. More importantly, DNMT1 knockdown induced the demethylation of Dok7 promoter, and enhanced the expression of Dok7 in gliomas. These results suggest that epigenetic silencing of Dok7 may provide a novel glioma treatment strategy.