Acquired resistance to temozolomide (TMZ) is a principal driver of therapeutic failure and tumour recurrence in glioblastoma (GBM). This study sought to elucidate the molecular underpinnings of this resistance, aiming to identify viable prognostic markers and therapeutic targets to refine personalized treatment strategies. We integrated gene expression and clinical data from the GEO, TCGA, and CGGA databases. A multipronged approach combining bioinformatics screening with in vitro and in vivo experiments was employed to elucidate the role and mechanism of the candidate gene F13A1 in GBM malignancy and chemoresistance. Our analysis identified F13A1 as a gene whose elevated expression compared with that in lower-grade gliomas or normal tissue strongly correlated with adverse prognosis and higher pathological grade in GBM. The results of functional assays demonstrated that F13A1 knockdown markedly attenuated the proliferative, migratory, and invasive capacities of GBM cells, while they were also resensitized to TMZ. Conversely, F13A1 overexpression resulted in the opposite phenotype, significantly enhancing these malignant traits and increasing TMZ resistance. Mechanistically, pathway enrichment analyses linked F13A1 to epithelial–mesenchymal transition (EMT) and NF-κB signalling. We further established that F13A1 inhibition suppressed both EMT progression and NF-κB pathway activation, thereby counteracting malignant behaviour and drug resistance. Notably, TNF-α stimulation effectively rescued the sh-F13A1-mediated phenotype, confirming the involvement of this pathway. Our findings collectively indicate that F13A1 facilitates GBM aggression and TMZ resistance through the NF-κB-driven induction of EMT. These results suggest that F13A1 is a compelling prognostic biomarker and promising candidate for targeted therapeutic intervention in GBM.

Acquired resistance to chemotherapy, especially to temozolomide (TMZ), is a major challenge correlated with the treatment failure of glioblastoma (GBM). Stanniocalcin-1 (STC1) is a glycoprotein hormone involved in multiple biological processes in cancer cells. However, the function and underlying mechanism of STC1 in GBM still remain unclear. To this end, exploring the potential functional role and mechanism of STC1 inducing TMZ resistance becomes an urgent need for individual individualized strategies for GBM. The GSE151680 dataset was obtained from the GEO database; thus, bioinformatic analysis was performed by using R software (version 4.2.0) to screen the differentially expressed genes correlated to TMZ resistance in GBM. Cox regression and nonnegative matrix factorization (NMF) analysis were conducted to establish a prognostic model. Additionally, immunohistochemistry (IHC) staining, qRT-PCR, and western blot were used to investigate the expression of STC1 in GBM tissues and non-tumor controls. Mechanically, loss-of-function and gain-of-function assays were performed to validate the biological functions of STC1 on the malignant biological characters and TMZ resistance of GBM cells. Besides, the enrichment analysis was performed to investigate the downstream pathway of STC1. In this study, STC1 was selected as the gene candidate correlated to TMZ resistance according to the results of Cox regression and NMF analysis. Additionally, increased expression of STC1 could be observed in GBM and was significantly correlated to poor prognosis in GBM. Besides, multiple malignant characters including proliferation, migration, invasion, tumorigenesis, and TMZ resistance of GBM could be markedly reduced by exogenous downregulation of STC1; contrarily, overexpression of STC1 promoted the malignant behaviors and drug resistance of GBM cells. Moreover, GO, KEGG, and GSEA analysis revealed that STC1 induced epithelial-mesenchymal transition (EMT) via activation of NF-κB signaling. Furthermore, the treatment of TNF-α (an activator of the NF-κB pathway) partially reversed the inhibitory effect of sh-STC1 on the proliferation and metastasis in GBM cells. In conclusion, STC1 induced EMT thus enhances the malignancies and drug resistance of GBM cells by activating the NF-κB pathway, providing new evidence for clinical drug development in GBM.

BACKGROUND:Augmented reality (AR) has been widely used in neurosurgery in recent years. The combination of AR and brain surface morphology for localization has not been reported. The aim of this work was to report the outcomes of combined method for locating supratentorial lesions in neurosurgery. METHODS:After multimodal image registration, brain tissue, the lesion, and blood vessels were reconstructed using a three-dimensional Slicer. AR was conducted using a smartphone application named Persp three-dimensional to project intracranial lesions on the scalp. The incision and size of the craniotomy were designed according to the location of the lesions. After craniotomy, the lesions were precisely located using brain surface morphology. Three types of morphology were used to localize the lesions: 1) the morphology of sulci and gyri; 2) superficial cerebral veins; and 3) combination of both. Then, the lesions were resected. Postoperative magnetic resonance imaging confirmed the extent of the resection. RESULTS:Of the 34 patients included in this study, 13 (38.2%) had gliomas, 15 (44.1%) had focal cortical dysplasia, and 6 (17.6%) had cavernous hemangiomas. The first type of morphology was used in 8 (23.5%) patients, the second type in 5 (14.7%), and the third in 21 (61.8%). In all cases, the lesions were accurately located and completely removed. No complications were recorded. CONCLUSIONS:AR combined with brain surface morphology could accurately locate lesions. This combined approach is convenient to use, and helpful for planning craniotomy and removing lesions.

ObjectivesThis study aimed to investigate the efficacy of using a newly formulated magnesium-rich artificial cerebrospinal fluid (MACSF) as an alternative to normal saline (NS) for intraoperative irrigation during aneurysm clipping in improving the prognosis of patients with Aneurysmal subarachnoid hemorrhage (aSAH).MethodsPatients with aSAH who underwent intraoperative irrigation with MACSF or NS during the clipping in the First Affiliated Hospital of Xi ‘an Jiaotong University from March 2019 to March 2022 were selected as MACSF group and NS group, respectively. The primary prognostic indicators were the incidence of favorable outcomes (mRS 0–2). The secondary outcome measures included cerebral vasospasm (CVS), mortality, total hospital stay, and intensive care unit (ICU) stay. Safety was evaluated based on the occurrence rates of hypermagnesemia, meningitis, and hydrocephalus.ResultsOverall, 34 and 37 patients were enrolled in the MACSF and NS groups, respectively. At 90 days after aSAH onset, the proportion of favorable prognosis in the MACSF group was significantly higher than that in the NS group (p = 0.035). The incidence of CVS within 14 days after surgery was significantly lower in the MACSF group than that in the NS group (p = 0.026). The mortality rate in the MACSF group was significantly lower than in the NS group (p = 0.048). The median lengths of hospital stay (p = 0.008) and ICU stay (p = 0.018) were significantly shorter in the MACSF group than in the NS group. No significant differences were observed in safety measures.ConclusionUsing MACSF as an irrigation fluid for aneurysm clipping can significantly improve the 90-day prognosis of patients with aSAH, which may be related to the reduced incidence of CVS.Clinical trial registrationhttps://www.clinicaltrials.gov, identifier NCT04358445.

This study was designed to dissect the function of plasmacytoma variant translocation 1 (PVT1) in hippocampal neuron injury in epilepsy and its possible molecular basis. Status epilepticus (SE) mouse model was built and primary hippocampal neurons were isolated. qRT-PCR and Western blot were applied to quantify the levels of related genes and proteins. Cell proliferation and apoptosis were examined by CCK-8, EdU, and flow cytometry assays. Inflammatory factors were detected using ELISA analysis. Dual-luciferase reporter and RIP assays were carried out to validate the relationship between miR-206-3p and PVT1 or CAMK4. PVT1 and CAMK4 were increased, and miR-206-3p was downregulated in the hippocampus and hippocampal neurons of SE mice. Knockdown of PVT1 or CAMK4 abated SE-induced proliferation inhibition, apoptosis, and inflammation in hippocampal neurons. Mechanistically, PVT1 could sponge miR-206-3p to upregulate the expression of CAMK4 in hippocampal neurons. Moreover, downregulation of miR-206-3p reversed the inhibitory effects of PVT1 knockdown on SE-induced apoptosis and inflammation in hippocampal neurons. Similarly, overexpression of CAMK4 abolished miR-206-3p-evoked arrest of apoptosis and inflammation in hippocampal neurons under SE condition. Collectively, PVT1 contributed to SE-induced apoptosis and inflammation in hippocampal neurons by modulating the miR-206-3p/CAMK4 axis, offering a novel insight into the prevention of epilepsy.

Background:Studies have shown that Nicotinamide adenine dinucleotide (NAD+) metabolism can promote the occurrence and development of glioma. However, the specific effects and mechanisms of NAD+ metabolism in glioma are unclear and there were no systematic researches about NAD+ metabolism related genes to predict the survival of patients with glioma.Methods:The research was performed based on expression data of glioma cases in the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Firstly, TCGA-glioma cases were classified into different subtypes based on 49 NAD+ metabolism-related genes (NMRGs) by consensus clustering. NAD+ metabolism-related differentially expressed genes (NMR-DEGs) were gotten by intersecting the 49 NMRGs and differentially expressed genes (DEGs) between normal and glioma samples. Then a risk model was built by Cox analysis and the least shrinkage and selection operator (LASSO) regression analysis. The validity of the model was verified by survival curves and receiver operating characteristic (ROC) curves. In addition, independent prognostic analysis of the risk model was performed by Cox analysis. Then, we also identified different immune cells, HLA family genes and immune checkpoints between high and low risk groups. Finally, the functions of model genes at single-cell level were also explored.Results:Consensus clustering classified glioma patients into two subtypes, and the overall survival (OS) of the two subtypes differed. A total of 11 NAD+ metabolism-related differentially expressed genes (NMR-DEGs) were screened by overlapping 5,995 differentially expressed genes (DEGs) and 49 NAD+ metabolism-related genes (NMRGs). Next, four model genes, PARP9, BST1, NMNAT2, and CD38, were obtained by Cox regression and least absolute shrinkage and selection operator (Lasso) regression analyses and to construct a risk model. The OS of high-risk group was lower. And the area under curves (AUCs) of Receiver operating characteristic (ROC) curves were >0.7 at 1, 3, and 5 years. Cox analysis showed that age, grade G3, grade G4, IDH status, ATRX status, BCR status, and risk Scores were reliable independent prognostic factors. In addition, three different immune cells, Mast cells activated, NK cells activated and B cells naive, 24 different HLA family genes, such as HLA-DPA1 and HLA-H, and 8 different immune checkpoints, such as ICOS, LAG3, and CD274, were found between the high and low risk groups. The model genes were significantly relevant with proliferation, cell differentiation, and apoptosis.Conclusion:The four genes, PARP9, BST1, NMNAT2, and CD38, might be important molecular biomarkers and therapeutic targets for glioma patients.

Glioblastoma (GBM) is one of the most lethal primary brain tumor with a poor median survival less than 15 months. Despite the development of the clinical strategies over the decades, the outcomes for GBM patients remain dismal due to the strong proliferation and invasion ability and the acquired resistance to radiotherapy and chemotherapy. Therefore, developing new biomarkers and therapeutic strategies targeting GBM is in urgent need. In this study, gene expression datasets and relevant clinical information were extracted from public cancers/glioma datasets, including TCGA, GRAVENDEEL, REMBRANDT, and GILL datasets. Differentially expressed genes were analyzed and NEK2 was picked as a candidate gene for subsequent validation. Human tissue samples and corresponding data were collected from our center and detected by immunohistochemistry analysis. Molecular biological assays and in vivo xenograft transplantation were performed to confirm the bioinformatic findings. High-throughput RNA sequencing, followed by KEGG analysis, GSEA analysis and GO analysis were conducted to identify potential signaling pathways related to NEK2 expression. Subsequent mechanism assays were used to verify the relationship between NEK2 and NF-κB signaling. Overall, we identified that NEK2 is significantly upregulated in GBM and the higher expression of NEK2 exhibited a poorer prognosis. Functionally, NEK2 knockdown attenuated cell proliferation, migration, invasion, and tumorigenesis of GBM while NEK2 overexpression promoted the GBM progression. Furthermore, High-throughput RNA sequencing and bioinformatics analysis indicated that NEK2 was positively related to the NF-κB signaling pathway in GBM. Mechanically, NEK2 activated the noncanonical NF-κB signaling pathway by phosphorylating NIK and increasing the activity and stability of NIK. In conclusion, NEK2 promoted the progression of GBM through activation of noncanonical NF-κB signaling, indicating that NEK2- NF-κB axis could be a potential drug target for GBM.

Background:Lower-grade gliomas (LGGs) are characterized by remarkable genetic heterogeneity and different clinical outcomes. Classification of LGGs is improved by the development of molecular stratification markers including IDH mutation and 1p/19q chromosomal integrity, which are used as a hallmark of survival and therapy sensitivity of LGG patients. However, the reproducibility and sensitivity of the current classification remain ambiguous. This study aimed to construct more accurate risk-stratification approaches.Methods:According to bioinformatics, the sequencing profiles of methylation and transcription and imaging data derived from LGG patients were analyzed and developed predictable risk score and radiomics score. Moreover, the performance of predictable models was further validated.Results:In this study, we determined a cluster of 6 genes that were correlated with IDH mutation/1p19q co-deletion status. Risk score model was calculated based on 6 genes and showed gratifying sensitivity and specificity for survival prediction and therapy response of LGG patients. Furthermore, a radiomics risk score model was established to noninvasively assist judgment of risk score in pre-surgery. Taken together, a predictable nomogram that combined transcriptional signatures and clinical characteristics was established and validated to be preferable to the histopathological classification. Our novel multi-omics nomograms showed a satisfying performance. To establish a user-friendly application, the nomogram was further developed into a web-based platform: https://drw576223193.shinyapps.io/Nomo/, which could be used as a supporting method in addition to the current histopathological-based classification of gliomas.Conclusions:Our novel multi-omics nomograms showed the satisfying performance of LGG patients and assisted clinicians to draw up individualized clinical management.

Glioblastoma (GBM) is one of the most lethal types of primary brain tumors in adults with a median survival of less than 15 months. Although comprehensive clinical treatment strategies including surgical resection followed by radiotherapy and chemotherapy are widely applied, the prognosis for GBM patients remains dismal. The Nuclear Factor-κB (NF-κB) signaling pathway is a complex network linking extracellular stimuli to cell survival and proliferation, and aberrant activation of NF-κB signaling has been implicated in the propagation of a wide range of cancers. However, the underlying mechanism of NF-κB activation still requires further investigation. Here, we report that crumbs homolog 2 (CRB2) is markedly up-regulated in human GBM relative to non-tumor tissues or normal astrocytes. Clinically, enriched CRB2 could be observed in high grade glioma with IDH IDH wild-type and 1p19q co-deletion and implied poor outcome in GBM. Consistent with this, malignant characteristics of GBM cells including proliferation, migration, invasion and tumorigenesis were significantly suppressed by lentivirus knock-down of CRB2. Furthermore, exogenous overexpression of CRB2 enhanced the malignant biological signatures of GBM cells as well as therapy resistance to temozolomide (TMZ). To further investigate the molecular mechanisms responsible, bioinformatics analysis was performed using 3 public databases, with the result that CRB2 was found to correlate closely with tumor necrosis factor α (TNFα)–NF–κB signaling. Mechanistically, elevated CRB2 increased the phosphorylation of IκB-kinase α (IKKα), thus activating NF-κB via reduction of Ikβ protein. Taken together, these data suggest that CRB2 might be a reliable prognostic biomarker and potential therapeutic target for GBM.

"大健康"是根据时代发展、社会需求与疾病谱的改变提出的一种全局理念,医学人才的培养正是推进"大健康"时代的关键生产力.如何推进医学教育改革、提高医学人才质量,已经成为我国现阶段高等医学教育改革的核心.笔者通过在美国及德国医学院访问学习的经历,将中、美、德医学教育体系进行比较分析,进而总结美、德医学教育模式中值得借鉴之处,以期能够促进我国医学卓越人才的培养.

Nonglioblastomatous diffuse glioma (non-GDG) is a heterogeneous neuroepithelial tumor that exhibits a varied survival range from 4 to 13 years based on the diverse subtypes. Recent studies demonstrated novel molecular markers can predict prognosis for non-GDG patients; however, these findings as well as pathological classification strategies show obvious limitations on malignant transition due to the heterogeneity among non-GDGs. Therefore, developing reliable prognostic biomarkers and therapeutic targets have become an urgent need for precisely distinguishing non-GDG subtypes, illuminating the underlying mechanism. Nuclear factor κβ (NF-κB) has been proved to be a significant nuclear transcriptional regulator with specific DNA-binding sequences to participate in multiple pathophysiological processes. However, the underlying mechanism of NF-κB activation still needs to be further investigated. Herein, our results indicated retinol-binding protein 1 (RBP1) was significantly upregulated in the IDHWT and 1p19qNon co-del non-GDG subtypes and enriched RBP1 expression was markedly correlated with more severe outcomes. Additionally, malignant signatures of the non-GDG cells including proliferation, migration, invasion, and self-renewal were significantly suppressed by lentiviral knockdown of RBP1. To further explore the underlying molecular mechanism, bioinformatics analysis was performed using databases, and the results demonstrated RBP1 was strongly correlated with tumor necrosis factor α (TNFα)-NF-κB signaling. Moreover, exogenous silencing of RBP1 reduced phosphorylation of IkB-kinase α (IKKα) and thus decreased NF-κB expression via decreasing the degradation of the IκBα protein. Altogether, these data suggested RBP1-dependent activation of NF-κB signaling promoted malignancy of non-GDG, indicating that RBP1 could be a reliable prognostic biomarker and potential therapeutic target for non-GDG.

Low‐grade gliomas (LGGs) are grade III gliomas based on the WHO classification with significant genetic heterogeneity and clinical properties. Traditional histological classification of gliomas has been challenged by the improvement of molecular stratification; however, the reproducibility and diagnostic accuracy of LGGs classification still remain poor. Herein, we identified fatty acid binding protein 5 (FABP5) as one of the most enriched genes in malignant LGGs and elevated FABP5 revealed severe outcomes in LGGs. Functionally, lentiviral suppression of FABP5 reduced malignant characters including proliferation, cloning formation, immigration, invasion and TMZ resistance, contrarily, the malignancies of LGGs were enhanced by exogenous overexpression of FABP5. Mechanistically, epithelial‐mesenchymal transition (EMT) was correlated to FABP5 expression in LGGs and tumour necrosis factor α (TNFα)‐dependent NF‐κB signalling was involved in this process. Furthermore, FABP5 induced phosphorylation of inhibitor of nuclear factor kappa‐B kinase α (IKKα) thus activated nuclear factor kappa‐B (NF‐κB) signalling. Taken together, our study indicated that FABP5 enhances malignancies of LGGs through canonical activation of NF‐κB signalling, which could be used as individualized prognostic biomarker and potential therapeutic target of LGGs.

INTRODUCTION:Glioblastoma (GBM) is identified as a lethal malignant tumor derived from the nervous system. Despite the standard clinical strategy including maximum surgical resection, temozolomide (TMZ) chemotherapy, and radiotherapy, the median survival of GBM patients remains <15 months. Accumulating evidence indicates that rapid-acquired radioresistance is one of the most common reasons for GBM recurrence. Therefore, developing novel therapeutic targets for radioresistant GBM could yield long-term cures.AIMS:To investigate the functional role of CXCL1 in the acquired radioresistance and identify the molecular pathway correlated to CXCL1.RESULTS:In this study, we identified that CXCL1 is highly expressed in GBM and the elevation of CXCL1 is involved in radioresistance and poor prognosis in GBM patients. Additionally, silencing CXCL1 attenuated the proliferation and radioresistance of GBM cells. Furthermore, we demonstrated that CXCL1-overexpression induced radioresistance through mesenchymal transition of GBM via the activation of nuclear factor-kappa B (NF-κB) signaling.CONCLUSION:CXCL1 was highly enriched in GBM and positively correlated with poor prognosis in GBM patients. Additionally, elevated CXCL1 induced radioresistance in GBM through regulation of NF-κB signaling by promoting mesenchymal transition in GBM.

The original version of this article unfortunately contained a mistake in the AuthorGroup section.

Background Glioma has the characteristics of high incidence and mortality, and is a common malignant tumor of the central nervous system. Circular RNAs (circRNAs) have been reported to play vital roles in progression of cancer including glioma, and circKIF4A is up-regulated in glioma tissues. However, its role and mechanisms in gliomas are unclear. Methods circKIF4A and miR-139-3p were determined by qRT-PCR. Transwell assay, wound-healing assay, cell colony formation and flow cytometry were performed to measure cell invasion, migration, proliferation and apoptosis. Western blotting was used to evaluate Wnt/β-catenin pathway-related protein. Luciferase reporter assays confirmed the relationship among circKIF4A, miR-139-3p and Wnt5a. Sphere formation was performed to measure the ability of glioma-initiating cells (GICs) spheroid formation. A nude mouse xenograft model was established and immunohistochemical staining was used to detect Ki-67 and Wnt5a levels. Results circKIF4A and Wnt5a were up-regulated and miR-139-3p was down-regulated in both glioma cells and tissues. circKIF4A promoted Wnt5a expression by sponging miR-139-3p. Knockdown of circKIF4A inhibited the colony formation ability, migration and invasion, and promoted the apoptosis of glioma cells by regulating miR-139-3p. Knockdown of circKIF4A inhibited Wnt/β-catenin signaling pathway and proliferation-related signal via miR-139-3p. Furthermore, knockdown of circKIF4A or overexpression of miR-139 suppressed the ability of sphere formation of GICs and inhibitd Wnt/β-catenin signaling pathway and proliferation-related signal in GICs. Additionally, depletion of circKIF4A decreased the expression level of Wnt5a and Ki-67, inhibited tumorigenesis in xenograft modes. Conclusion circKIF4A was overexpressed in glioma, and knockdown of circKIF4A suppressed glioma progression via miR-139-3p/Wnt5a axis. The results indicated that circKIF4A may be a potential target for clinical treatment of glioma.

BackgroundGlioblastoma (GBM) is a lethal type of primary brain tumor with a median survival less than 15 months. Despite the recent improvements of comprehensive strategies, the outcomes for GBM patients remain dismal. Accumulating evidence indicates that rapid acquired chemoresistance is the major cause of GBM recurrence thus leads to worse clinical outcomes. Therefore, developing novel biomarkers and therapeutic targets for chemoresistant GBM is crucial for long-term cures. MethodsTranscriptomic profiles of glioblastoma were downloaded from gene expression omnibus (GEO) and TCGA database. Differentially expressed genes were analyzed and candidate gene PLK2 was selected for subsequent validation. Clinical samples and corresponding data were collected from our center and measured using immunohistochemistry analysis. Lentiviral transduction and in vivo xenograft transplantation were used to validate the bioinformatic findings. GSEA analyses were conducted to identify potential signaling pathways related to PLK2 expression and further confirmed by in vitro mechanistic assays. ResultsIn this study, we identified PLK2 as an extremely suppressed kinase-encoding gene in GBM samples, particularly in therapy resistant GBM. Additionally, reduced PLK2 expression implied poor prognosis and TMZ resistance in GBM patients. Functionally, up-regulated PLK2 attenuated cell proliferation, migration, invasion, and tumorigenesis of GBM cells. Besides, exogenous overexpression of PLK2 reduced acquired TMZ resistance of GBM cells. Furthermore, bioinformatics analysis indicated that PLK2 was negatively correlated with Notch signaling pathway in GBM. Mechanically, loss of PLK2 activated Notch pathway through negative transcriptional regulation of HES1 and degradation of Notch1.ConclusionLoss of PLK2 enhances aggressive biological behavior of GBM through activation of Notch signaling, indicating that PLK2 could be a prognostic biomarker and potential therapeutic target for chemoresistant GBM.

目的:研究法舒地尔联用尼莫地平对蛛网膜下腔出血(SAH)后脑血管痉挛的疗效.方法:SAH后脑血管痉挛患者92例纳入研究,随机分为单药组和联合组,各46例.在常规治疗的基础上,单药组给与尼莫地平治疗,联合组给与尼莫地平联用法舒地尔治疗,均治疗14 d.比较2组治疗有效率,治疗前后格拉斯哥昏迷量表(GCS)评分、大脑中动脉的血流速度、格拉斯哥预后量表(GOS)评分,血清核转录因子κB(NF-κB)和基质金属蛋白酶-9(MMP-9)水平及不良反应发生率.结果:联合组总有效率为86.96％,高于单药组的69.56％(P<0.05);2组治疗后GCS评分明显升高,大脑中动脉的血流速度明显降低(均P<0.05),且联合组改善幅度大于单药组(均P<0.05);治疗后1个月联合组的GOS评分为(4.95±0.73)分,明显高于单药组的(4.02±0.43)分(均P<0.05);2组治疗后的血清NF-κB和MMP-9水平均明显降低(均P<0.05),且联合组低于单药组(P<0.05);2组不良反应发生率差异无统计学意义(P>0.05).结论:法舒地尔联用尼莫地平对SAH后脑血管痉挛的效果明显优于单用尼莫地平.

目的 探讨脑胶质瘤患者血清microRNA-375(miRNA-375)水平及其临床意义.方法 选择2012年1月—2013年12月西安交通大学第一附属医院神经外科收治的脑胶质瘤患者120例作为脑胶质瘤组,选取同期该院健康体检群众120例作为对照组.逆转录聚合酶链反应测定患者血清miRNA-375水平,对两组患者的临床资料进行比较分析.结果 脑胶质瘤组miRNA-375相对表达量低于对照组(P<0.05).术前KPS评分≥80分、病理分级Ⅲ和Ⅳ级患者血清miRNA-375水平低于术前KPS评分<80分、病理分级Ⅰ和Ⅱ级患者(P<0.05).Logistics回归分析显示,血清miRNA-375水平与脑胶质瘤术前KPS评分[Ol^R=8.794(95 CI:2.016,18.426),P=0.000]和病理分级[Ol^R=9.314(95 CI:2.413,20.319),P=0.000]相关.低表达miRNA-375患者总生存时间、无进展生存时间低于高表达miRNA-375患者(P<0.05).结论 脑胶质瘤患者血清miRNA-375水平降低,血清miRNA-375水平与脑胶质瘤KPS评分和病理分级有关,有望成为脑胶质瘤诊断和预后判断的潜在标志物.

目的 研究miRNA-491(miR-491)对胶质母细胞瘤细胞上皮间质转化和凋亡的调控作用和机制.方法 收集新鲜胶质瘤(glioblastoma multiforme,GBM)13例和对应的癌旁组织(nontumorous tissues,NT)13例.体外培养神经胶质细胞(nor-mal human astrocytes,NHA)和神经胶质母细胞瘤细胞U-87 MG和U-118 MG.将U-118MG细胞分为无处理组(control)、miR-491的拟似物转染组(mimic)、mimic阴性对照组(mimic-NC)和mimic联合表达 αB-crystallin组(mimic+αB-crystallin).CCK-8法评估细胞增殖,RT-qPCR和或Western blot检测miR-491、αB-crystallin、Twist1、E-cadherin、N-cadherin、Bax、Bcl-2的表达.荧光素酶报告基因验证miR-491和 αB-crystallin基因3′UTR区的结合.结果 GBM组织与NT组织比较,U-87 MG和U-118 MG分别与NHA比较,miR-491显著降低(P<0.05).与control组比较,mimic组 αB-crystallin、N-cadherin、Twist1的表达水平下调,细胞凋亡率上调(P<0.05),E-cadherin的水平上调(P<0.05).荧光素酶报告结果证实miR-491与 αB-crystallin基因3′UTR区的结合.mimic+αB-crystallin组部分逆转mimic对于凋亡标记物和上皮间质转化标记物的表达(P<0.05).结论miR-491抑制胶质母细胞瘤细胞的上皮间质转化且促进细胞凋亡,miR-491负调控 αB-crystallin是其关键分子机制之一.

Objective The aim of this study was to investigate the expression of cell cycle checkpoint kinase 1(Chk1)gene in glioblastoma cells( GBM) and its correlation with GBM cell proliferation,tumorigenic activity and prognosis. Methods The ex-pression of Chk1 in GBM cells was selected and analyzed by TCGA database and brain tumor molecular database( Rembrandt),and the level of Chk1 expression in GBM cells was detected by molecular biology techniques such as Western blot and Real-Time PCR. The expression of Chk1 was silenced by siRNA to investigate its effect on proliferation and colony-forming ability of GBM cells. The prognosis survival of GBM patients accompanying with Chk1 expression was analyzed by immunohistochemical staining and Rembrandt database. Results The results of TCGA database and Rembrandt showed that Chk1 gene was highly expressed in GBM tissues. West-ern blot and Real-Time PCR also showed that Chk1 gene was highly expressed in GBM cells. Lentiviral transfection siRNA-specific silencing of Chk1 significantly inhibited proliferation and colony-forming ability of U87 cells( P<0. 01 and P<0. 05). Prognostic survival analysis showed that GBM patients with low expression of Chk1 gene had a significantly better clinical outcome than those of GBM patients with high expression of Chk1 gene(P<0. 001). Conclusion Chk1 gene is overexpressed in GBM cells,up-regula-tion of Chk1 gene expression can promote the growth and proliferation of GBM cells,and Chk1 gene is associated with poor prognosis in GBM patients.