Glioma Cell Growth Research Articles

Wilforol A inhibits human glioma cell proliferation and deactivates the PI3K/AKT signaling pathway.

To study the anti-proliferation activity of wilforol A against glioma cells and its possible molecular mechanisms. Human glioma cell lines U118 MG and A172, human tracheal epithelial cells (TECs) and astrocytes (HAs) were exposed to various concentrations of wilforol A and evaluated for viability, apoptosis, and levels of proteins using WST-8 assay, flow cytometry and Western blot analysis, respectively. Wilforol A inhibited the growth of U118 MG and A172 cells, but not TECs and HAs, in a concentration-dependent manner and the estimated IC50 were 6 to 11 μM after 4 h-exposure. Apoptosis was induced at an apoptotic rate of about 40% at 100 μM in U118 MG and A172 cells, but the rates were less than 3% in TECs and HAs. Co-exposure to caspase inhibitor Z-VAD-fmk significantly reduced wilforol A-induced apoptosis. Wilforol A treatment also reduced the colony formation ability of U118 MG cells and triggered a significant increase in ROS production. Elevated levelsof pro-apoptotic proteins p53, Bax and cleaved caspase 3 and reduced level of the anti-apoptotic protein Bcl-2 were observed in glioma cells exposed to wilforol A. The expression of PI3K and p-Akt genes in the PI3K/AKT pathways were significantly downregulated in glioma cellstreated with wilforol A. Wilforol A inhibits the growth of glioma cells, reduces the levels of proteins in the P13K/Akt signal transduction pathways and increases the levels of pro-apoptotic proteins.

P53 inhibits the Urea cycle and represses polyamine biosynthesis in glioma cell lines.

Glioma is the most common malignant tumor of the central nervous system. The urea cycle (UC) is an essential pathway to convert excess nitrogen and ammonia into the less toxic urea in humans. However, less is known about the functional significance of the urea cycle in glioma. p53 functions as a tumor suppressor and modulates several cellular functions and disease processes. In the present study, we aimed to explore whether p53 influences glioma progression by regulating the urea cycle. Here, we demonstrated the inhibitory impact of p53 on the expression of urea cycle enzymes and urea genesis in glioma cells. The level of polyamine, a urea cycle metabolite, was also regulated by p53 in glioma cells. Carbamoyl phosphate synthetase-1 (CPS1) is the first key enzyme involved in the urea cycle. Functionally, we demonstrated that CPS1 knockdown suppressed glioma cell proliferation, migration and invasion. Mechanistically, we demonstrated that the expression of ornithine decarboxylase (ODC), which determines the generation of polyamine, was regulated by CPS1. In addition, the impacts of p53 knockdown on ODC expression, glioma cell growth and aggressive phenotypes were significantly reversed by CPS1 inhibition. In conclusion, these results demonstrated that p53 inhibits polyamine metabolism by suppressing the urea cycle, which inhibits glioma progression.

Induction of apoptosis in glioma cells by lycorine via reactive oxygen species generation and regulation of NF-κB pathways.

Glioma is an extremely aggressive primary brain tumor, which is highly resistant to chemotherapy, presenting a therapeutic challenge. Here, we explored the anti-glioma effects and the underlying mechanism of lycorine, an isoquinoline alkaloid isolated from lycoris on glioma cells. We found that lycorine could dose dependently inhibit C6 glioma cell growth and induce cell apoptosis and intracellular reactive oxygen species (ROS) production. The half-maximal inhibitory concentration (IC50) values of lycorine on C6 glioma cells at 48h was 2.85μM. Meanwhile, lycorine treatment caused dysfunction of the NF-κB signal, as demonstrated by the up-regulation of NF-κB inhibitor protein IκB and the downregulation of the NF-κB phosphorylation protein p-p65. The addition of NF-κB inhibitor SC75741 further confirmed the importance of the NF-κB pathway in lycorine-induced cell-growth inhibition. Moreover, lycorine might act synergically with temozolomide (TMZ) to reduce drug resistance by blocking the NF-κB pathway. Our study suggested that lycorine exerts an anti-glioma effect by inducing ROS production and inhibiting NF-κB, which validated that lycorine may be a potential candidate for glioma treatment alone or in combination with TMZ.

Enantioselective theranostics of brain glioma using chiral quantum structures

CdSe/CdS dot-in-rods (DRs) tailored by chiral biomolecules are promising candidates for biological theranostics. The authors of this study synthesised chiral CdSe/CdS DRs with different sizes using the post-ligand-exchange method. Their high-resolution imaging and cytotoxicity performances were investigated, respectively. The results suggested that the chiral cysteine coverage strategy could significantly enhance the biocompatibility of CdSe/CdS DRs in bioimaging and bioimaging-guided therapies. Numerous photodynamic and chemodynamic therapy studies for brain glioma cells demonstrated enantioselective efficacy, wherein chiral DRs could exhibit improved oxygen species and hydroxyl radical generations under corresponding circularly polarised light radiation. d-DRs with right-handed circularly polarised light activation could generally present 3.14/1.5 times higher efficacy than left-handed or linearly polarised light irradiated samples. Wound-healing assay/migration and invasion assays asserted that the applications of chiral DRs could suppress the infiltrative growth and metastasis of glioma cells by reducing the migration and invasion ability by nearly 50%. In vivo experiments also confirmed that d-DRs exerted more substantial enhanced permeability and retention (EPR) effects in the tumour tissue, leading to better bioimaging ability and efficient tumour ablation. Such adjuvant approaches would be a viable alternative to cancer treatments with a high possibility of recurrence and poor prognosis.

Marine halophyte derived polyphenols inhibit glioma cell growth through mitogen-activated protein kinase signaling pathway

Plants that are pharmacologically significant require intensive phytochemical characterization for bioactive profiling of the compounds, which has enabled their safe use in ayurvedic medicine. The present study is focused on the phytochemical analyses, quantitative estimation and profiling of secondary metabolites of leaf extract, as well as the antioxidant and cytotoxic activity of the potent halophytes such as Avicennia marina, Ceriops tagal, Ipomoea pes-caprae, and Sonneratia apetala. The in vitro antioxidant property was investigated using DPPH, ferric reducing antioxidant capacity (FRAP) assay. Bioactive compounds such as phenols, flavonoids, saponin and alkaloids were quantitatively estimated from the extracts of A.marina, C.tagal, I.pes-capra and S.apetala, which possessed higher phenol content than the other studied halophytes. The extracts at 200 µg/ml revealed higher antioxidant activity than the standard ascorbic acid and it functions as a powerful oxygen free radical scavenger with 77.37%, 75.35% and 72.84% for S.apetala, I.pes-caprae and C.tagal respectively and with least IC50 for I.pes-caprae (11.95 µg/ml) followed by C.tagal (49.94 µg/ml). Cell viability and anti-proliferative activity of different polyphenolic fractions of C.tagal (CT1 and CT2) and I.pes-caprae fraction (IP) against LN229, SNB19 revealed Ipomoea as the promising anti-cytotoxic fraction. IP-derived polyphenols was further subjected to apoptosis, migration assay, ROS and caspase − 3 and − 7 to elucidate its potentiality as a therapeutic drug. IP-polyphenols was found to have higher percentage of inhibition than the CT1 and CT2 polyphenols of C.tagal on comparison with TMZ. All the above-mentioned in-vitro analysis further validated the ability of IP-polyphenols inducing cell death via ROS-mediated caspase dependent pathway. Further, proteomic and phospho-proteomic analysis revealed the potential role of IP-polyphenols in the regulation of cell proliferation through MMK3, p53, p70 S6 kinase and RSK1 proteins involved in mitogen-activated protein kinase signaling pathway. Our analysis confirmed the promising role of I.pes-caprae derived polyphenols as an anti-metastatic compound against GBM cells.

Theoretical and numerical analysis of a parabolic system with chemoattraction modeling the growth of glioma cells

In this paper, we consider a two dimensional PDE model describing the proliferation-invasion structure of hypoxic glial cells in the brain, in which the cell movement is determined not only by natural diffusion but also, by the gradient of the concentration of oxygen. This model is given by a second order nonlinear system involving the density of cancer cells and the oxygen concentration, which are coupled by a chemoattraction term, a source of logistic growth, and a reaction term of Michaelis-Menten type. The contribution of this paper is summarized in the following two main aspects: first, we prove the existence and uniqueness of strong solutions; and second, we propose a nonlinear fully discrete finite element (FE) approximation for the model. We prove its well-posedness, some uniform estimates, the positivity for the discrete oxygen concentration and approximated positivity for the discrete tumour cells, which are required in this biological model. The key point to develop the numerical analysis is to control properly the second order nonlinear chemotaxis term as well as to obtain a discrete energy estimate which, in particular, gives a bounded energy; this energy estimate is derived by using a regularization technique. Finally, we present some numerical simulations which allow us to validate the theoretical results obtained.

Up-Regulation of miR-26a-5p Promoted Cell Growth and Tumor Metastasis of Intracranial Malignancy Through Phosphatase and Tensin Homolog Deleted on Chromosome Ten/Phosphatidylinositol3-Kinase/Protein Kinase B Signaling Pathway

Objective: Intracranial malignancy has ranked the 6th and 3rd in terms of global tumor morbidity and mortality, respectively. MicroRNA (miRNA) can regulate the cell physiological process. Methods: In previous study, we explored the anti-cancer effects and mechanism of miR-26a-5p in human glioma. MiR-26a-5p expression was increased in patient with glioma. Up-regulation of miR-26a-5p promoted cell growth and tumor metastasis of human glioma through inactivation of PTEN/PI3K/Akt. Results: Down-regulation of miR-26a-5p reduced cell growth and tumor metastasis of human glioma. Downregulation of miR-26a-5p induced PTEN protein expression, and reduced PI3K and p-Akt protein expression in human glioma. PTEN or PI3K inhibitor reduced the effects of miR-26a-5p on cell growth and tumor metastasis of human glioma. Conclusion: Our findings proved that the cancer effect of MiR-26a-5p regulates PTEN expression and promoted cell growth of human glioma through PI3K/Akt signalling pathway.

Lactobacillus casei enhances the apoptosis inducing effect of geniposide on U87 human glioma cells in vitro

The goal of this work was to clarify the mechanism of action of Lactobacillus casei on genipin in triggering glioma apoptosis. DPPH and ABTS free radicals could be successfully eliminated by geniposide, LC-NBRC101979 (Lactobacillus casei), and geniposide + LC-NBRC101979. Geniposide and LC-NBRC101979 had effects that were stronger when combined than when taken alone. Geniposide, LC-NBRC101979, and Geniposide + LC-NBRC101979 did not have any detrimental effects on healthy epithelial cells HBE, but they greatly decreased the growth of U87 glioma cells, according to cell studies. Additionally, the combination of geniposide and LC-NBRC101979 had a stronger inhibitory impact than either drug alone. Results from qPCR revealed that in U87 cells, geniposide, LC-NBRC101979, and eniposide + LC-NBRC101979 could up-regulate caspase-3, COX-2, p53, c-myc, p21 mRNA expression and down-regulate Bcl-2, NF-κB expression. According to the results of the study on the effects of oxidative stress on cells, geniposide, LC-NBRC101979, and geniposide combined with LC-NBRC101979 can decrease the levels of MDA, LDH, and NO in normally damaged epithelial cells caused by oxidative stress and increase the levels of CAT, SOD, GSH-Px, and T-AOC. According to HPLC data, LC-NBRC101979 was able to convert the majority of geniposide into geniposide. It is clear that LC-NBRC101979 may enhance geniposide's inhibitory impact on glioma.

Retracted: Cannabinoid WIN 55,212-2 Inhibits Human Glioma Cell Growth by Triggering ROS-Mediated Signal Pathways.

[This retracts the article DOI: 10.1155/2021/6612592.].

FAM72A promotes glioma progression by regulating mitophagy through the Pink1/Parkin signaling pathway.

Background: There is growing evidence that aberrant expression of FAM72A contributes to biological dysfunction, especially mitochondrial dysfunction. However, its role in most tumors remains unclear, especially in glioma. Methods: Herein, a high-throughput sequencing approach was used here to identify FAM72A as the target molecule. Next, we detected the protein and mRNA expression levels of FAM72A in normal brain tissue (NBT) as well as different grades of glioma tissue. CCK-8, colony formation, Transwell assays, and Western blotting, were all used to determine the molecular effects of FAM72A on glioma cells. Results: FAM72A was significantly upregulated in glioma, was significantly correlated with WHO grade and was associated with poor clinical outcomes. In functional assays, FAM72A was shown to promote glioma cell growth. Subsequent mechanistic studies indicated that FAM72A promoted glioma progression by regulating mitophagy through the Pink1/Parkin signaling pathway. In addition, FAM72A promoted mitophagy and maintained Pink1 stability through the Pink1/Parkin signaling pathway. Finally, FAM72A promoted tumor immune escape by upregulating PD-L1 expression. Conclusion: All of these data indicate that FAM72A confers an aggressive phenotype and poor prognosis on gliomas. Targeting FAM72A might represent a new therapeutic strategy for glioma.

G protein inhibitory α subunit 2 is a molecular oncotarget of human glioma.

Identification of novel therapeutic oncotargets for human glioma is extremely important. Here we tested expression, potential functions and underlying mechanisms of G protein inhibitory α subunit 2 (Gαi2) in glioma. Bioinformatics analyses revealed that Gαi2 expression is significantly elevated in human glioma, correlating with poor patients' survival, higher tumor grade and wild-type IDH status. Moreover, increased Gαi2 expression was also in local glioma tissues and different glioma cells. In primary and immortalized (A172) glioma cells, Gαi2 shRNA or knockout (KO, by Cas9-sgRNA) potently suppressed viability, proliferation, and mobility, and induced apoptosis. Ectopic Gαi2 overexpression, using a lentiviral construct, further augmented malignant behaviors in glioma cells. p65 phosphorylation, NFκB activity and expression of NFκB pathway genes were decreased in Gαi2-depleted primary glioma cells, but increased following Gαi2 overexpression. There was an increased binding between Gαi2 promoter and Sp1 (specificity protein 1) transcription factor in glioma tissues and different glioma cells. In primary glioma cells Gαi2 expression was significantly reduced following Sp1 silencing, KO or inhibition. In vivo studies revealed that Gαi2 shRNA-expressing AAV intratumoral injection hindered growth of subcutaneous glioma xenografts in nude mice. Moreover, Gαi2 KO inhibited intracranial glioma xenograft in nude mice. Gαi2 depletion, NFκB inhibition and apoptosis induction were observed in subcutaneous and intracranial glioma xenografts with Gαi2 depletion. Together, overexpressed Gαi2 is important for glioma cell growth possibly by promoting NFκB cascade activation.

Small molecule-mediated disruption of ribosome biogenesis synergizes with FGFR inhibitors to suppress glioma cell growth.

High-grade gliomas are malignant brain tumors characterized by aggressiveness and resistance to chemotherapy. Prognosis remains dismal, highlighting the need to identify novel molecular dependencies and targets. Ribosome biogenesis (RiBi), taking place in the nucleolus, represents a promising target as several cancer types rely on high RiBi rates to sustain proliferation. Publicly available transcriptomics data of glioma patients revealed a positive correlation between RiBi rates and histological grades. We, therefore, hypothesized that glioma cells could be susceptible to RiBi inhibition. Transcriptomics data from glioma patients were analyzed for RiBi-related processes. BMH-21, a small molecule inhibitor of RNA pol I transcription, was tested in adult and pediatric high-grade glioma cell lines and a zebrafish transplant model. Cellular phenotypes were evaluated by transcriptomics, cell cycle analysis, and viability assays. A chemical synergy screen was performed to identify drugs potentiating BMH-21-mediated effects. BMH-21 reduced glioma cell viability, induced apoptosis, and impaired the growth of transplanted glioma cells in zebrafish. Combining BMH-21 with TMZ potentiated cytotoxic effects. Moreover, BMH-21 synergized with Fibroblast Growth Factor Receptor (FGFR) inhibitor (FGFRi) Erdafitinib, a top hit in the chemical synergy screen. RiBi inhibition using BMH-21, POLR1A siRNA, or Actinomycin D revealed engagement of the FGFR-FGF2 pathway. BMH-21 downregulated FGFR1 and SOX2 levels, whereas FGF2 was induced and released from the nucleolus. This study conceptualizes the implementation of RiBi inhibition as a viable future therapeutic strategy for glioma and reveals an FGFR connection to the cellular response upon RiBi inhibition with potential translational value.

Encouraging probiotics for the prevention and treatment of immune-related adverse events in novel immunotherapies against malignant glioma.

Among the malignant tumors in the central nervous system (CNS), glioma is the most challenging tumor to the public society, which accounts for the majority of intracranial malignant tumors with impaired brain function. In general, conventional therapies are still unable to provide an effective cure. However, novel immunotherapies have changed the treatment scene giving patients a greater potential to attain long term survival, improved quality of life. Having shown favorable results in solid tumors, those therapies are now at a cancer research hotspot, which could even shrink the growth of glioma cells without causing severe complications. However, it is important to recognize that the therapy may be occasionally associated with noteworthy adverse action called immune-related adverse events (IRAEs) which have emerged as a potential limitation of the therapy. Multiple classes of mediators have been developed to enhance the ability of immune system to target malignant tumors including glioma but may also be associated with the IRAEs. In addition, it is probable that it would take long time after the therapy to exhibit severe immune-related disorders. Gut microbiota could play an integral role in optimal immune development and/or appropriate function for the cancer therapy, which is a vital component of the multidirectional communication between immune system, brain, and gut, also known as gut-brain-immune axis. Here, we show the potential effects of the gut-brain-immune axis based on an "engram theory" for the innovative treatment of IRAEs.

Lipid Alterations in Glioma: A Systematic Review.

Gliomas are highly lethal tumours characterised by heterogeneous molecular features, producing various metabolic phenotypes leading to therapeutic resistance. Lipid metabolism reprogramming is predominant and has contributed to the metabolic plasticity in glioma. This systematic review aims to discover lipids alteration and their biological roles in glioma and the identification of potential lipids biomarker. This systematic review was conducted using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Extensive research articles search for the last 10 years, from 2011 to 2021, were conducted using four electronic databases, including PubMed, Web of Science, CINAHL and ScienceDirect. A total of 158 research articles were included in this study. All studies reported significant lipid alteration between glioma and control groups, impacting glioma cell growth, proliferation, drug resistance, patients' survival and metastasis. Different lipids demonstrated different biological roles, either beneficial or detrimental effects on glioma. Notably, prostaglandin (PGE2), triacylglycerol (TG), phosphatidylcholine (PC), and sphingosine-1-phosphate play significant roles in glioma development. Conversely, the most prominent anti-carcinogenic lipids include docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and vitamin D3 have been reported to have detrimental effects on glioma cells. Furthermore, high lipid signals were detected at 0.9 and 1.3 ppm in high-grade glioma relative to low-grade glioma. This evidence shows that lipid metabolisms were significantly dysregulated in glioma. Concurrent with this knowledge, the discovery of specific lipid classes altered in glioma will accelerate the development of potential lipid biomarkers and enhance future glioma therapeutics.

MCM4 is a novel prognostic biomarker and promotes cancer cell growth in glioma

Gliomas account for 75% of all primary malignant brain tumors in adults and result in high mortality. Accumulated evidence has declared the minichromosome maintenance protein complex (MCM) gene family plays a critical role in modulating the cell cycle and DNA replication stress. However, the biological function and clinic characterization of nine MCM members in low-grade glioma are not yet clarified. In this study, we utilized diverse public databases, including The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Rembrandt, Human Protein Atlas (HPA), Linkedomics, cbioportal, Tumor and Immune System Interaction Database (TISIDB), single-sample GSEA (ssGSEA), Tumor Immune Estimation Resource (TIMER), Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Therapeutics Response Portal databases to explore the mRNA and protein expression profiles, gene mutation, clinical features, diagnosis, prognosis, signaling pathway, tumor mutational burden (TMB), immune subtype, immune cell infiltration, immune modulator and drug sensitivity of nine MCMs. Afterward, qRT-PCR was utilized to detect the expression of the MCM family in glioblastoma multiforme (GBM) cell lines. The one-, three-, or five-year survival rate was predicted by utilizing a nomogram established by cox proportional hazard regression. In this study, we found that nine MCMs were consistently up-regulated in glioma tissues and glioma cell lines. Elevated nine MCMs expressions were significantly correlated with a higher tumor stage, isocitrate dehydrogenase (IDH) mutates, 1p/19q codeletion, histological type, and primary therapy outcome. Survival analyses showed that higher expression of MCM2-MCM8 (minichromosome maintenance protein2-8) and MCM10 (minichromosome maintenance protein 10) were linked with poor overall survival (OS) and progression-free survival (PFS) in glioma patients. On the other hand, up-regulated MCM2-MCM8 and MCM10 were significantly associated with shorter disease-specific survival (DSS) in glioma patients. Univariate and multivariate analyses revealed that MCM2 (minichromosome maintenance protein2), MCM4 (minichromosome maintenance protein 4), MCM6 (minichromosome maintenance protein 6), MCM7 (minichromosome maintenance protein 7) expression and tumor grade, 1p/19q codeletion, age, and primary therapy outcome were independent factors correlated with the clinical outcome of glioma patients. More importantly, a prognostic MCMs model constructed using the above five prognostic genes could predict the overall survival of glioma patients with medium-to-high accuracy. Furthermore, functional enrichment analysis indicated that MCMs principal participated in regulating cell cycle and DNA replication. DNA copy number variation (CNV) and DNA methylation significantly affect the expression of MCMs. Finally, we uncover that MCMs expression is highly correlated with immune cell infiltration, immune modulator, TMB, and drug sensitivity. In summary, this finding confirmed that MCM4 is a potential target of precision therapy for patients with glioma.

TMIC-07. PYK2 SIGNALING IS UPREGULATED IN RECURRENT GLIOBLASTOMA TUMORS IN C57BL/6/GL261 GLIOMA IMPLANTATION MODEL

Abstract Glioblastoma (GBM) is the most aggressive type of brain cancer with no successful treatment available. Microglia makes up to 30% of total GBM tumor mass. Previously we demonstrated that microglia within the tumor stimulate glioma cell growth and invasion through the proline rich tyrosine kinase 2 (Pyk2). Tumor resection is the first line treatment for GBM. Our previous studies with use of mouse glioma implantation model indicate that microglia in a site of tumor resection undergo significant modulations in cytokines expression profile. We hypothesize that microglia activated by tumor resection induces Pyk2 signaling in glioma cell and promotes malignant properties of the tumor cells that fail to be eliminated by resection. Using C57BL/6/GL261 mouse glioma implantation model, we analyzed primary implanted tumors and re-grown tumor after surgical resection. Two weeks after glioma cells implantation, tumor resection was performed, and two weeks later regrown tumors were used for western blot analysis. Total Pyk2 and phosphorylated Pyk2[Y579/50] were analyzed. The study revealed that Pyk2 phosphorylation is upregulated in re-grown tumor compared to primary implanted tumor. Treatment with PF-562271 (Pyk2/FAK inhibitor, once/daily, 50mg/kg, orally) beginning the 2ndday after tumor resection, reduced Pyk2 phosphorylation in regrown tumors compared to animals that did not receive treatment with PF-562271. In conclusion we can state that tumor resection procedure induces the upregulation of Pyk2 phosphorylation in regrown tumors. This effect is eliminated with oral administration of PF-562271.

CSIG-40. STEAROYL-COA DESATURASE 1 (SCD1) IS REQUIRED FOR WNT SIGNALING TO INDUCE AN APOPTOSIS IN IDH MUTANT GLIOMA

Abstract BACKGROUND AND HYPOTHESES SCD1, a major enzyme of saturated fatty acids, has been implicated to be important for tumor metabolic reprograming. Our previous study show that a high level of SCD1 mRNA is associated with IDH1mut lower grade gliomas. IDH1mut glioma cells are more sensitive to SFA induced apoptosis. However, the underlying mechanism remains unclear. In this study, we investigate the functions of SCD1 in IDHmut glioma and the potential contribution of SCD1 for cancer therapy of glioma. STUDY DESIGN AND METHODS The genetically engineered IDH wild-type, IDHmut and patient derived glioma cell lines were used to evaluate SCD1 functions. The expression of proteins were checked by Western-blotting assay. SCD1 was silenced by CRISPR or siRNA. The transcriptome change after SCD1 knockdown was profiled by RNA-seq or single cell RNA-seq (scRNA-seq). RESULTS AND CONCLUSIONS SCD1 transient silencing slowed down the cell growth, suggesting that SCD1 may possess an oncogenic property. RNA-seq analysis revealed that SCD1 inhibition decreased the expression of wnt-signaling pathway genes in IDH-1mut cells. scRNA confirmed that CRISPR SCD1 significantly decreased wnt signaling in the patient cell line Ts603. Therefore, we activated wnt pathway using a small chemical compound, BML-2838. Consistent with recent studies, wnt pathway induction led to a dramatically suppression of glioma cells growth. However, SCD1 silencing reversed this inhibitory effect. Further investigation revealed that SCD1 inhibition reduced the nucleus translocation of phosphorylated beta-catenin. Overall, the results suggest that SCD1 is vital for the onset of wnt pathway in glioma cells. High level of SCD1 expression may render the IDHmut glioma cells more sensitive to wnt pathway induced apoptosis. RELEVANCE AND IMPORTANCE In clinical, the 5-years survival rate of glioma remains low. SCD1 have been considered as a target for glioma therapy, recently. Our data provides a new insight on the strategy to target SCD1 in clinical.

Propofol inhibits glioma progression by regulating circMAPK4/miR-622/HOXA9 axis.

Propofol has a tumor-suppressive role in glioma, but the mechanism by which propofol is involved in glioma progression is largely unknown. This study aims to explore a potential circular RNAs (circRNAs)/microRNAs (miRNAs)/mRNA network in response to Propofol in glioma. Human glioma cell lines (U251 and LN229) were suffered from Propofol treatment (5μg/mL for 24h) and transfection. circRNA mitogen-activated protein kinase 4 (circMAPK4), miR-622, homeobox A9 (HOXA9) abundances were determined by quantitative reverse transcription polymerase chain reaction and western blot. Migration and invasion were analyzed via transwell analysis. Cell proliferation was evaluated using Cell Counting Kit-8 and colony formation analysis. Cell apoptosis and related protein expression were determined via flow cytometry and western blot. Target relationship was assessed via dual-luciferase reporter analysis, RNA pull-down and RNA immunoprecipitation. Propofol reduced circMAPK4 expression. Propofol inhibited cell proliferation, migration and invasion, while increased apoptosis via decreasing circMAPK4 in glioma cells. miR-622 was targeted via circMAPK4. circMAPK4 knockdown decreased glioma cell growth, migration and invasion by up-regulating miR-622. miR-622 knockdown reversed the effect of Propofol on glioma progression. HOXA9 was targeted by miR-622, and its expression was decreased by Propofol treatment. miR-622 overexpression restrained glioma progression via decreasing HOXA9. Propofol regulated circMAPK4/miR-622/HOXA9 axis in glioma cells. Propofol constrains glioma progression by regulating circMAPK4/miR-622/HOXA9 axis in vitro. Propofol restrains glioma cell growth, migration and invasion. circMAPK4 can regulate HOXA9 by sponging miR-622 in glioma cells. Propofol represses glioma progression via a circMAPK4/miR-622/HOXA9 axis.

Down-regulation of CX43 expression by miR-1 inhibits the proliferation and invasion of glioma cells.

Connexin (CX) 43 makes glioblastoma resistant to temozolomide, the first-line chemotherapy drug. However, targeting CX43 is very difficult because the mechanisms underlying CX43-mediated resistance remain unclear. CX43 is highly expressed in glioblastoma, which is closely associated with poor prognosis and chemotherapy resistance. The present study was to analyze the mechanism of microRNA (miR)-1 in regulating the proliferation and invasion of glioma cells. The effects of knockdown of miR-1 on the growth of glioma cell lines were observed by establishing blank, miR-1 inhibitor, and miR-1 mimic groups. Cell proliferation was detected using a Cell Counting Kit-8 (CCK-8) assay, cell apoptosis was detected by flow cytometry, and protein expression was detected by western blot. We used the Student's t-test to assess continuous data between the two groups and the Kruskal-Wallis test was adopted for multiple group comparisons. Compared with the mimics normal control (NC) group, the apoptosis rate of the miR-1-3p mimics group was decreased, while that of the miR-1-3p inhibitor group was increased compared to the inhibitor NC group. In addition, the miR-1-3p mimics model of U251 cells exerted an inhibitory effect on the invasion ability of cells, whereas the miR-1-3p inhibitor model of U251 cells showed an invasion-promoting effect. The dual-luciferase assay showed that miR-1-3p had a targeted relationship with the CX43 gene. Down-regulation of CX43 expression by miR-1 inhibited the infiltration and growth of glioma cells and further promoted the apoptosis of glioma cells by regulating CX43 expression.

MicroRNA-512-5p Derived from Bone Marrow Mesenchymal Stem Cells Suppresses Metastasis of Glioma Cells

Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) are enriched in microRNA-512-5p (miR-512-5p) expression and can inhibit glioma cell growth, but the mechanism is not clear. This study assesses how BMSC-miR-512-5p functions in glioma cells to provide evidence for treatment of glioma. Exosomes were collected from BMSCs to measure miR-512-5p level. Glioma cells SHG-44 were transfected with BMSC-miR-512-5p and KLF15 inhibitor followed by analysis of cell invasion by transwell and scratch assays, LF15 protein expression and the relation between miR-512-5p and KLF15. miR-512-5p expression in exosomes was higher than glioma cells. Transfection of miR-512-5p derived from BMSCs decreased cell migration and invasion decreased the number of migrated and invaded cells. Combination of miR-512-5p and KLF15 inhibitor further decreased cell migration and invasion. Furthermore, miR-512-5p was confirmed to target KLF15 gene as show by a decreased luciferase activity. In conclusion, BMSCs secrete exosomes to encapsulate miR-512-5p, which inhibits KLF15 gene expression to exert an inhibitory effect on the invasion and migration of glioma cells.