Pterional Craniotomy With Anterior Clinoidectomy for the Resection of a Sphenoid Ridge Meningioma: A Case Report and Two-Dimensional Operative Video.

The pterional craniotomy with anterior clinoidectomy is a surgical technique used to resect sphenoid ridge meningiomas. It involves drilling the bone of the anterior clinoid process to gain access to the skull base, including the cavernous sinus and petrous apex particularly. This approach offers several advantages, including excellent exposure of the surgical site, minimal brain retraction, and the ability to visualize and protect critical neurovascular structures. We present a case of a 59-year-old woman presented with headache, dizziness, blurry vision, and unsteady gait for several months. The brain magnetic resonance imaging with gadolinium contrast showed a large space-occupying homogeneously-enhancing lesion at the left skull base, displacing the surrounding structures, including the frontal lobe, temporal lobe, and brainstem. Herein, we present the intraoperative video on a case in which the pterional craniotomy with anterior clinoidectomy that can allow the exposure and resection of the tumor extending into the posterior fossa was utilized for the resection of a large left sphenoid ridge meningioma with brain stem compression.

MEX3A Impairs DNA Mismatch Repair Signaling and Mediates Acquired Temozolomide Resistance in Glioblastoma.

MutS protein homolog 2 (MSH2) is a key element involved in the DNA mismatch repair (MMR) system, which is responsible for recognizing and repairing mispaired bases. Simultaneously, MSH2 identifies DNA adducts induced by temozolomide (TMZ) and triggers apoptosis and autophagy in tumor cells. Previous work has revealed that reduced MSH2 expression is often observed in patients with glioblastoma (GBM) who relapse after chemotherapy. Elucidation of the mechanism behind TMZ-mediated reduction of MSH2 could help improve GBM treatment. Here, we report significant upregulation of Mex-3 RNA binding family member A (MEX3A) in GBM tissues and cell lines following TMZ treatment. MEX3A bound to the MEX3 recognition element (MRE) of MSH2 mRNA, which in turn recruited CCR4-NOT complexes to target MSH2 mRNA for deadenylation and degradation. In addition, ectopic expression of MEX3A significantly decreased cellular DNA MMR activities and reduced the chemosensitivity of GBM cells via downregulation of MSH2, while depletion of MEX3A sensitized GBM cells to TMZ. In MGMT-deficient patients with GBM, MEX3A expression correlated with MSH2 levels, and high MEX3A expression was associated with poor prognosis. Overall, these findings reveal a potential mechanism by which MSH2 expression is reduced in post-TMZ recurrent GBM. SIGNIFICANCE: A MEX3A/CCR4-NOT/MSH2 axis plays a crucial role in promoting temozolomide resistance, providing new insights into the function of MEX3A and suggesting MEX3A as a potential therapeutic target in therapy-resistant glioblastoma.

Efficient Dye Contaminant Elimination and Simultaneously Electricity Production via a Bi-Doped TiO2 Photocatalytic Fuel Cell.

TiO2 develops a higher efficiency when doping Bi into it by increasing the visible light absorption and inhibiting the recombination of photogenerated charges. Herein, a highly efficient Bi doped TiO2 photoanode was fabricated via a one-step modified sol-gel method and a screen-printing technique for the anode of photocatalytic fuel cell (PFC). A maximum degradation rate of 91.2% of Rhodamine B (RhB) and of 89% after being repeated 5 times with only 2% lost reflected an enhanced PFC performance and demonstrated an excellent stability under visible-light irradiation. The excellent degradation performance was attributed to the enhanced visible-light response and decreased electron-hole recombination rate. Meanwhile, an excellent linear correlation was observed between the efficient photocurrent of PFC and the chemical oxygen demand of solution when RhB is sufficient.

Imipramine impedes glioma progression by inhibiting YAP as a Hippo pathway independent manner and synergizes with temozolomide.

Patients with malignant glioma often suffered from depression, which leads to an increased risk of detrimental outcomes. Imipramine, an FDA-approved tricyclic antidepressant, has been commonly used to relieve depressive symptoms in the clinic. Recently, imipramine has been reported to participate in the suppression of tumour progression in several human cancers, including prostate cancer, colon cancer and lymphomas. However, the effect of imipramine on malignant glioma is largely unclear. Here, we show that imipramine significantly retarded proliferation of immortalized and primary glioma cells. Mechanistically, imipramine suppressed tumour proliferation by inhibiting yes-associated protein (YAP), a recognized oncogene in glioma, independent of Hippo pathway. In addition to inhibiting YAP transcription, imipramine also promoted the subcellular translocation of YAP from nucleus into cytoplasm. Consistently, imipramine administration significantly reduced orthotopic tumour progression and prolonged survival of tumour-bearing mice. Moreover, exogenous overexpression of YAP partially restored the inhibitory effect of imipramine on glioma progression. Most importantly, compared with imipramine or temozolomide (TMZ) monotherapy, combination therapy with imipramine and TMZ exhibited enhanced inhibitory effect on glioma growth both in vitro and in vivo, suggesting the synergism of both agents. In conclusion, we found that tricyclic antidepressant imipramine impedes glioma progression by inhibiting YAP. In addition, combination therapy with imipramine and TMZ may potentially serve as promising anti-glioma regimens, thus predicting a broad prospect of clinical application.

The Prevalence of Dental Anxiety Associated with Pain among Chinese Adult Patients in Guangzhou.

Background: Anxious people appear to exaggerate the severity of aversive experiences such as anxiety and pain. Anxiety towards dental procedures is a common difficulty that may be experienced by dental patients all over the world. The goal of the study is to find out the prevalence of dental anxiety and its associated factors in Chinese adult patients. Methods: A cross-sectional study was conducted on 183 dental adult patients whose age ranged from 18 to 70 years. Demographic details, first and most recent dental visits with experience, the MDAS, and the Visual Analogue Scale for Anxiety (VAS-A) were obtained. Data were analyzed by frequency analysis, chi-square test, and Spearman correlation test. Results: Most of the respondents were female (68.9%) and 30-45 years age group. The mean total score for dental anxiety on the MDAS was 13.63 (3.1). 80.3% of participants suffered from moderate or high dental anxiety. Age must show a strong association with dental anxiety among the participants (p=0.011). The first dental visit experience, the frequency of the dental visit, most recent dental experience, length of time since the most recent dental visit, and postponement of the dental visit are strongly associated with the MDAS score (p=0.001). Conclusions: The MDAS score exhibits that Chinese adult patients have significant dental anxiety and phobia. Identifying patients with dental anxiety as soon as possible is essential to providing better dental care.

TGF-ß1 modulates temozolomide resistance in glioblastoma via altered microRNA processing and elevated MGMT.

BACKGROUND: Our previous studies have indicated that miR-198 reduces cellular methylguanine DNA methyltransferase (MGMT) levels to enhance temozolomide sensitivity. Transforming growth factor beta 1 (TGF-ß1) switches off miR-198 expression by repressing K-homology splicing regulatory protein (KSRP) expression in epidermal keratinocytes. However, the underlying role of TGF-ß1 in temozolomide resistance has remained unknown. METHODS: The distribution of KSRP was detected by western blotting and immunofluorescence. Microarray analysis was used to compare the levels of long noncoding RNAs (lncRNAs) between TGF-ß1-treated and untreated cells. RNA immunoprecipitation was performed to verify the relationship between RNAs and KSRP. Flow cytometry and orthotopic and subcutaneous xenograft tumor models were used to determine the function of TGF-ß1 in temozolomide resistance. RESULTS: Overexpression of TGF-ß1 contributed to temozolomide resistance in MGMT promoter hypomethylated glioblastoma cells in vitro and in vivo. TGF-ß1 treatment reduced cellular MGMT levels through suppressing the expression of miR-198. However, TGF-ß1 upregulation did not affect KSRP expression in glioma cells. We identified and characterized 2 lncRNAs (H19 and HOXD-AS2) that were upregulated by TGF-ß1 through Smad signaling. H19 and HOXD-AS2 exhibited competitive binding to KSRP and prevented KSRP from binding to primary miR-198, thus decreasing miR-198 expression. HOXD-AS2 or H19 upregulation strongly promoted temozolomide resistance and MGMT expression. Moreover, KSRP depletion abrogated the effects of TGF-ß1 and lncRNAs on miR-198 and MGMT. Finally, we found that patients with low levels of TGF-ß1 or lncRNA expression benefited from temozolomide therapy. CONCLUSIONS: Our results reveal an underlying mechanism by which TGF-ß1 confers temozolomide resistance. Furthermore, our findings suggest that a novel combination of temozolomide with a TGF-ß inhibitor may serve as an effective therapy for glioblastomas.

Analgesic and Antibiotic Prescription Pattern among Dentists in Guangzhou: A Cross-Sectional Study.

Aim: To assess the rational use of drugs and the pattern of prescribing of analgesics and antibiotics for dental management and the information given by dentists in Guangzhou to their patients about the use of these drugs. Methods: A questionnaire was distributed to 225 dentists working in Guangzhou. The questionnaires consisted of open-ended questions and were given to dentists about analgesic and antibiotic use in dentistry. The questionnaires were analyzed, and absolute frequencies were expressed in the answers to each question. The cases, the analgesics, and the antibiotics recommended by the dentists for each case were determined by the frequency analysis method of descriptive statistics. Results: Responses to the questionnaire were received from 164 (72.9%) dentists. Paracetamol and diclofenac were the most widely prescribed analgesics. It is also estimated that selective COX-2 inhibitors or opioid analgesics have not been administered by dentists. The antibiotics primarily used for treatment were amoxicillin and metronidazole, and amoxicillin was used for prophylaxis. While more than 80% of dentists indicated that they provided their patients with information on the use of antibiotics, the quality of the information was limited. Patients were primarily instructed by dentists to observe the dosage and dose intervals of the prescription drugs. Conclusions: The results of the present study demonstrated that dentists most commonly prescribe paracetamol and diclofenac as analgesics, amoxicillin, and metronidazole for the therapy of periodontal, endodontic, and surgical procedures. The results also showed that dentists informed their patients inadequately about analgesic and antibiotic use.

Effects of Long Form of CAPON Overexpression on Glioma Cell Proliferation are Dependent on AKT/mTOR/P53 Signaling.

Background: CAPON has two isoforms in human brain: long form of CAPON (CAPON-L) and short form of CAPON (CAPON-S). Recent studies have indicated the involvement of CAPON in tumor cell growth. We aimed to reveal the role of the two CAPON isoforms in the proliferation of glioma cells in this study. Materials and Methods: Lentivirus-mediated stable cell lines with CAPON-L or CAPON-S overexpression were established in U87 and U251 glioma cells. Cell counting kit-8 and colony formation assays were used to evaluate cell proliferation. Western blot analysis of cell cycle-related proteins and flow cytometry were performed to analyze cell cycle progression. Some important molecules of the AKT/mTOR pathway and P53 were also measured by Western blot analysis. Results: Overexpression of CAPON-L showed a significantly inhibitory role in U251 cells, while it exhibited a promoting role in U87 cells. Consistently, overexpressing CAPON-L impeded the cell cycle progression and down-regulated the expression levels of Cyclin D1, CDK4 and CDK6 in U251 cells, whereas it up-regulated the CDK6 level in U87 cells. The overexpression of CAPON-L significantly decreased the phosphorylation and/or total levels of AKT, mTOR and S6 in U251 cells, while it did not affect these signaling molecules in U87 cells, except for a significant increase in the phosphorylation of AKT at Thr-308 site. Transfecting constitutively active AKT (myr-AKT) partially reversed the decreased phosphorylation of AKT and S6 in the CAPON-L-overexpressing U251 cells. In addition, we found a significant decrease in the wild-type P53 level in the CAPON-L-overexpressing U87 cells. The overexpression of CAPON-S also inhibited cell proliferation, blocked cell cycle progression, and decreased the AKT/mTOR pathway activity in U251 cells. Conclusion: The effects of CAPON-L overexpression on glioma cell proliferation are dependent on the AKT/mTOR/P53 activity. The overexpression of CAPON inhibits U251 cell proliferation through the AKT/mTOR signaling pathway, while overexpressing CAPON-L promoted U87 cell proliferation, possibly through down-regulating the P53 level.

Transparent conductive film based on silver nanowires and single-wall carbon nanotubes for transparent heating films.

In this paper, hybrid transparent conductive films (TCFs) are designed by combining silver nanowires with the single-wall carbon nanotubes (SWCNTs) and the transparent heating films (THFs) based on the TCFs are evaluated for possible vehicle applications. By comparing the properties, including the transmittance, sheet resistance, microstructure and heating curves, we found that the SWCNTs/AgNWs are considerably suitable for making THFs. The after-treatment methods, such as physical method (hot roll pressing) and chemical method (nitric acid and Poly (diallydimethylammonium chloride) solution, (PDAC)) were researched in detail to optimize the sheet resistance and transparency to fit the THF requirements. A careful study of the different after-treatment methods revealed that hot roll pressing can quickly and efficiently improve the properties, while the nitric acid is more helpful than PDAC for the long-term stability. The results showed that a small amount of SWCNTs addition can promote the endurable maximum electric current by spreading the heat fast and efficiently, and the maximum current flow can be as high as 4 A. The thermal stability of the THFs and the de-frog performance were tested, indicating that the hybrid film had an advantage in resisting current shock and good thermal efficiency was obtained. The fabricated TCFs of stable thermal properties are qualified as a windshield-glass heater.

Fstl1/DIP2A/MGMT signaling pathway plays important roles in temozolomide resistance in glioblastoma.

Temozolomide was recognized as the first-line therapy for glioblastoma to prolong the survival of patients noticeably, while recent clinical studies found that some patients were not sensitive to temozolomide treatment. The possible mechanisms seemed to be methylguanine-DNA-methyltransferase (MGMT), mismatch repair, PARP, etc. And the abnormal expression of MGMT might be the most direct factor. In this study, we provide evidence that Fstl1 plays a vital role in temozolomide resistance by sequentially regulating DIP2A protein distribution, H3K9 acetylation (H3K9Ac), and MGMT transcription. As a multifunctional protein widely distributed in cells, DIP2A cooperates with the HDAC2-DMAP1 complex to enhance H3K9Ac deacetylation, prevent MGMT transcription, and increase temozolomide sensitivity. Fstl1, a glycoprotein highly expressed in glioblastoma, competitively binds DIP2A to block DIP2A nuclear translocation, so as to hinder DIP2A from binding the HDAC2-DMAP1 complex. The overexpression of Fstl1 promoted the expression of MGMT in association with increased promoter H3K9Ac. Upregulation of Fstl1 enhanced temozolomide resistance, whereas Fstl1 silencing obviously sensitized GBM cells to temozolomide both in vivo and in vitro. Moreover, DIP2A depletion abolished the effects of Fstl1 on MGMT expression and temozolomide resistance. These findings highlight an important role of Fstl1 in the regulation of temozolomide resistance by modulation of DIP2A/MGMT signaling.

Delivery of MGMT mRNA to glioma cells by reactive astrocyte-derived exosomes confers a temozolomide resistance phenotype.

The glioma-astrocyte interaction plays an important role in tumor microenvironment remodeling; however, the underlying mechanism has not been completely clarified. In this study, we show that glioma cells stimulate normal human astrocyte (NHA) into reactive astrocyte (RAS) in a non-contact manner. Additionally, the amount of O6-alkylguanine DNA alkyltransferase (MGMT) mRNA in exosomes (EXOs) released by RAS was significantly increased compared with that in non-reactive NHA. Importantly, MGMT-negative glioma cells can take up RAS-EXOs and acquire a temozolomide (TMZ)-resistant phenotype via the translation of exogenous exosomal MGMT mRNA both in vitro and in vivo. Our findings illuminate a novel phenomenon that may be a potent mechanism underlying glioma recurrence in which glioma-associated NHAs protect MGMT-negative glioma cells from TMZ-induced apoptosis by the functional intercellular transfer of exosomal MGMT mRNA.

Fstl1 Promotes Glioma Growth Through the BMP4/Smad1/5/8 Signaling Pathway.

BACKGROUND: Gliomas result in the highest morbidity and mortality rates of intracranial primary central nervous system tumors because of their aggressive growth characteristics and high postoperative recurrence. They are characterized by genetic instability, intratumoral histopathological variability and unpredictable clinical behavior in patients. Proliferation is a key aspect of the clinical progression of malignant gliomas, complicating complete surgical resection and enabling tumor regrowth and further proliferation of the surviving tumor cells. METHODS: The expression of Fstl1 was detected by western blotting and qRT-PCR. We used cell proliferation and colony formation assays to measure proliferation. Then, flow cytometry was used to analyze cell cycle progression. The expression of Fstl1, p-Smad1/5/8 and p21 in GBM tissue sections was evaluated using immunohistochemical staining. Furthermore, we used coimmunoprecipitation (Co-IP) and immunoprecipitation to validate the relationship between Fstl1, BMP4 and BMPR2. Finally, we used orthotopic xenograft studies to measure the growth of tumors in vivo. RESULTS: We found that follistatin-like 1 (Fstl1) was upregulated in high-grade glioma specimens and that its levels correlated with poor prognosis. Fstl1 upregulation increased cell proliferation, colony formation and cell cycle progression, while its knockdown inhibited these processes. Moreover, Fstl1 interacted with bone morphogenetic protein (BMP) 4, but not BMP receptor (BMPR) 2, and competitively inhibited their association. Furthermore, Fstl1 overexpression suppressed the activation of the BMP4/Smad1/5/8 signaling pathway, while BMP4 overexpression reversed this effect. CONCLUSION: Our study demonstrated that Fstl1 promoted glioma growth through the BMP4/Smad1/5/8 signaling pathway, and these findings suggest potential new glioblastoma treatment strategies.

MicroRNA-520d-5p inhibits human glioma cell proliferation and induces cell cycle arrest by directly targeting PTTG1.

Glioma accounts for the majority of primary malignant brain tumors in adults and is highly aggressive. Although various therapeutic approaches have been applied, outcomes of glioma treatment remain poor. Acquiring a better understanding of the pathogenic mechanisms is essential to the design of effective therapeutic strategies. Previous studies have found that miR-520d-5p was negatively correlated with glioma grade, but its role and mechanism in glioma progression remain largely unknown. In the present study, we reported that miR-520d-5p directly targeted the Pituitary Tumor Transforming Gene 1 (PTTG1) and functioned as a tumor-suppressor in glioma. The expression of miR-520d-5p in glioma cells and specimens were detected by Quantitative reverse transcription-PCR and Fluorescence in situ hybridization (FISH). The effects of miR-520d-5p on glioma progression was examined by cell-counting kit 8, colony formation, 5-ethynyl-2-deoxyuridine (EDU) and flow cytometry assays. Using bioinformatics and luciferase reporter assays, we identified PTTG1 as a novel and direct target of miR-520d-3p. A xenograft model was used to study the effect of miR-520d-5p on tumor growth and angiogenesis. We found that miR-520d-5p expression was significantly decreased in glioma cell lines and tissues. Overexpression of miR-520d-5p showed a significant inhibitory effect on cell proliferation and accompanied cell cycle G0/G1 arrest in U87-MG and LN229 glioma cells. PTTG1 was a novel and direct target of miR-520d-5p, and the protein expression of PTTG1 was markedly reduced after overexpression of miR-520d-5p in U87-MG and LN229 cells. Overexpression of PTTG1 reversed the inhibitory effect of miR-520d-5p on glioma cell proliferation. In vivo studies confirmed that miR-520d-5p overexpression retarded the growth of U87 xenograft tumors, which was accompanied by reduced expression of PTTG1. In conclusion, these results provide compelling evidence that miR-520d-5p functions as an anti-onco-miRNA, which is important in inhibiting cell proliferation in GBM, and its anti-oncogenic effects are mediated chiefly through direct suppression of PTTG1 expression. Therefore, we suggest that miR-520d-5p is a potential candidate for the prevention of glioblastoma.

EZH2 alteration driven by microRNA-524-5p and microRNA-324-5p promotes cell proliferation and temozolomide resistance in glioma.

Recent data have been shown that EZH2 is a critical oncogene via the repression of tumor suppressor genes in human cancers. In our study, we performed a genome-wide miRNA screen with a bioinformatics analysis to identify EZH2 specific miRNAs. Of these miRNAs, miR-524-5p and miR-324-5p were decreased in glioma tissues, and confered poor prognosis for glioma patients. Upregulation of miR-524-5p and miR-324-5p reduced glioma cell proliferation and increased temozolomide (TMZ) chemosensitivity by targeting EZH2. Importantly, the effection of miR-524-5p and miR-324-5p on cell proliferation and TMZ chemosensitivity in glioma were reversed by expression of EZH2 cDNA. Further, miR-524-5p and miR-324-5p overexpression suppressed glioma growth and prolonged survival in an intracranial xenograft model. Multivariate Cox regression analysis revealed that miR-524-5p was an independent prognostic factor in gliobalstoma patients. Taken together, these data indicate that miRNA-driven EZH2 repression may provide evidence of the molecular mechanism for gliomagenesis and the novel therapeutic targets for glioma.

MicroRNA-141-3p promotes glioma cell growth and temozolomide resistance by directly targeting p53.

Glioblastoma multiforme is the most common primary malignancy in the brain and confers a uniformly poor prognosis. MicroRNAs have been shown to activate or inhibit tumorigenesis. Abnormalities in the p53 signaling pathway are found in various cancers and correlate with tumor formation. We examined the expression of microRNA-141-3p (miR-141-3p) in glioma of different grades by analysis of expression profiling databases and clinical specimens. Cell proliferation and flow cytometry assays were performed to evaluate the promotion of miR-141-3p in proliferation, cell cycle, apoptosis, and temozolomide resistance of glioblastoma cells in vitro. Bioinformatics analyses, luciferase reporter assays, and immunoblotting showed that p53 is a target gene of miR-141-3p. A significant inverse correlation was observed between expression of miR-141-3p and p53 in glioma and normal brain tissues (R2=0.506, P<0.0001). Rescue experiments indicated that overexpression of p53 significantly reversed the alterations in proliferation, cell cycle distribution, and temozolomide resistance measured by cell apoptosis induced by miR-141-3p overexpression. In an orthotopic mouse model of human glioma, inhibition of miRNA-141-3p reduced the proliferation and growth of glioma cells in the brain and significantly prolonged the survival of glioma-bearing mice. We suggest that miR-141-3p promotes glioblastoma progression and temozolomide resistance by altering p53 expression and therefore may serve as a new diagnostic marker and therapeutic target for glioma in the future.

Photoelectrocatalytic degradation of methylene blue using F doped TiO2 photoelectrode under visible light irradiation.

Photoelectrocatalysis (PEC) has attracted great interest due to cost effectiveness and high efficiency in water treatment. In this study, F doped TiO2 (F-TiO2) photoelectrodes with honeycomb like morphology were prepared, and the PEC performance was investigated. F-TiO2 particles that showed enhanced absorption of visible light were synthesized via a sol-gel method. F-TiO2 particles were anchored onto the surface of F-doped SnO2 glass by a screen-printing method to prepare the F-TiO2 photoelectrodes. The PEC performance of the F-TiO2 photoelectrodes was investigated via the degradation of methylene blue (MB) under visible light irradiation. The results show that the F-TiO2 photoelectrodes exhibited an excellent PEC performance that was affected by the F doping content, applied bias and solution pH. A maximum decolorization percentage of 97.8% was achieved by the FT-15 photoelectrode, with a 1.4 V bias at pH 9.94 after 4.0 h of visible light irradiation. The high PEC performance of the F-TiO2 photoelectrodes is mainly ascribed to the efficient separation of electron-hole (e--h+) pairs and the creation of active radicals such as hydroxyl radicals (OH). The PEC decolorization kinetic data were analyzed using the first-order kinetic model and the Langmuir-Hinshelwood (L-H) model. The data indicates that the PEC degradation of MB molecules mainly occurred on the surface of the F-TiO2 photoelectrodes, and the MB molecules were discolored mainly by h+ (41.5%) and OH (46.5%). In addition, 8.2% of the MB molecules were discolored by other oxidative species, and 3.8% of the MB molecules were discolored by self-sensitized oxidation.

CBX7 is a glioma prognostic marker and induces G1/S arrest via the silencing of CCNE1.

Chromobox homolog 7 (CBX7) cooperates with other polycomb group (PcG) proteins to maintain target genes in a silenced state. However, the precise role of CBX7 in tumor progression is still controversial. We found that the expression of CBX7 in four public databases was significantly lower in high grade glioma (HGG). The reduced expression of CBX7 correlated with poor outcome in HGG patients. Both KEGG and GO analyses indicated that genes that were negatively correlated to CBX7 were strongly associated with the cell cycle pathway. We observed that decreased CBX7 protein levels enhanced glioma cells proliferation, migration and invasion. Then, we verified that CBX7 overexpression arrested cells in the G0/G1 phase. Moreover, we demonstrated that the underlying mechanism involved in CBX7 induced repression of CCNE1 promoter requiring the recruitment of histone deacetylase 2 (HADC2). Finally, in vivo bioluminescence imaging and survival times of nude mice revealed that CBX7 behaved as a tumor suppressor in gliomas. In summary, our results validate the assumption that CBX7 is a tumor suppressor of gliomas. Moreover, CBX7 is a potential and novel prognostic biomarker in glioma patients. We also clarified that CBX7 silences CCNE1 via the combination of CCNE1 promoter and the recruitment of HDAC2.

MicroRNA-1468-5p inhibits glioma cell proliferation and induces cell cycle arrest by targeting RRM1.

MicroRNAs are associated with different types of cancers. In this study, we found that miR-1468-5p could inhibit growth and cell cycle progression in glioma by targeting ribonucleotide reductase large subunit M1 (RRM1). First, we analyzed miR-1468-5p expression in different glioma grades and the prognostic significance of its expression in glioblastoma multiform patients from the Chinese Glioma Genome Atlas. Then, we expressed miR-1468-5p in U87 and U251 cells and assessed the effects on proliferation and cell cycle progression using cell counting kit-8, colony formation, EdU and flow cytometry assays. Western blotting and luciferase reporter assays identified RRM1 as a novel direct target of miR-1468-5p. Experiments to determine the role of RRM1 in glioma showed that RRM1 expression was significantly higher in glioma than in normal brain tissues, and silencing RRM1 with small-interfering RNAs decreased proliferation and suppressed cell cycle progression, which indicated that RRM1 had pro-tumor functions. miR-1468-5p overexpression suppressed RRM1 expression, reduced glioma cell proliferation and induced cell cycle arrest, which was partially rescued by forced RRM1 expression. In summary, our study revealed that the regulatory mechanism of miR-1468-5p in glioma cell cycle progression involved direct regulation of RRM1 expression, suggesting that RRM1 may be a potential therapeutic target for glioma.

MicroRNA-1301 inhibits proliferation of human glioma cells by directly targeting N-Ras.

Glioma is one of the most common, rapidly progressive and fatal brain tumors, and accumulating evidence shows that microRNAs (miRNAs) play important roles in the development of cancers, including glioma. Therapeutic applications of miRNAs in Ras-driven glioma have been proposed; however, their specific functions and mechanisms are poorly understood. Here, we report that miR-1301-3p directly targets the neuroblastoma Ras viral oncogene homolog (N-Ras) and functions as a tumor-suppressor in glioma. Quantitative reverse transcription-PCR was applied to detect the expression of miR-1301-3p in glioma specimens. The direct target genes of miR-1301-3p were predicted by bioinformatic analysis and further verified by immunoblotting and luciferase assays. The effects of miR-1301-3p on the proliferation and cell cycle of glioma cells were analyzed by cell-counting kit 8, colony formation, 5-ethynyl-2-deoxyuridine (EDU) and flow cytometry assays. A xenograft model was used to study the effect of miR-1301-3p on tumor growth and angiogenesis. The expression levels of miR-1301-3p in glioma specimens were significantly downregulated. N-Ras was confirmed as a direct target of miR-1301-3p. MiR-1301-3p inhibited glioma cell growth and blocked the cell cycle to G1 by negatively regulating N-Ras and its downstream signaling pathway, MEK-ERK1/2. Furthermore, the inhibitory effects of miR-1301-3p could be rescued by the overexpression of N-Ras. The protein levels of N-Ras were up-regulated in clinical glioma specimens and were negatively correlated with miR-1301-3p expression levels (r=-056, P=0.0002). In vivo studies revealed that increased levels of miR-1301-3p delayed the growth of intracranial tumors, which was accompanied by decreased Ki67 and CD31 expression. Taken together, our results demonstrate that miR-1301-3p plays a significant role in inactivating the Ras signaling pathway through the inhibition of N-Ras, which may provide a novel therapeutic strategy for treatment of glioma and other Ras-driven cancers.

Polycomb group expression signatures in the malignant progression of gliomas.

Polycomb group (PcG) proteins form at least two key complexes, namely polycomb repressive complex 1 and polycomb repressive complex 2. These complexes are involved in the progression of various cancers. Systematic research has not been conducted on the aberrant expression of PcG members in gliomas. Using the Chinese Glioma Genome Atlas data set, PcG expression patterns between normal brain tissues and glioma samples were analyzed, and a PcG-based classifier was then developed using BRB Cox regression and risk-score model. These results were validated in an independent GSE16011 set. A total of six PcGs [chromobox protein homolog (CBX) 6, CBX7, PHD finger protein 1, enhancer of zeste homolog 2 (EZH2), DNA (cytosine-5-)-methyltransferase 3ß (DNMT3B) and polyhomeotic-like protein 2] were identified to be associated with glioma grade. Survival analysis then revealed a five-PcG gene signature one protective gene (enhancer of zeste homolog 1) and four risky genes (EZH2, PHD finger protein 19, DNMT3A and DNMT3B), which may identify patients with high risk of poor prognosis of glioma. Multivariate Cox analysis indicated that the five-PcG signature was an independent prognostic biomarker. These findings indicated that a novel prognostic classifier, five-PcG signature, served as an independent prognostic marker for patients with glioma.