INTRODUCTION:Intracerebral hemorrhage (ICH) is a serious neurological event and a potentially fatal complication among patients with cancer; however, the mortality patterns of cancer involving ICH remain inadequately characterized. METHODS:This study analyzed trends and disparities in cancer mortality involving ICH in the United States from 1999 to 2020 using the CDC WONDER database. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated for deaths with cancer as the underlying cause and documented ICH as a contributing cause. Temporal trends were evaluated using Joinpoint regression to estimate annual percent changes (APCs) and average annual percent changes (AAPCs), with corresponding 95% confidence intervals (CIs). RESULTS:A total of 26,652 cancer deaths involving ICH were identified. The overall AAMR declined from 0.48 per 100,000 in 1999 to 0.34 in 2020 (AAPC -1.55; 95% CI -1.93 to -1.05). Mortality rates were consistently higher among males, individuals aged ≥65 years, Black individuals, and residents of the Midwest. Although AAMRs decreased across all demographic groups, declines were slower among males, older adults, White individuals, and residents of the South. Across cancer subtypes, hematologic, respiratory and intrathoracic, and central nervous system cancers exhibited the highest mortality burden. Digestive system cancers were the only subtype with a significant long-term increase (AAPC 2.11; 95% CI 0.66 to 3.65). CONCLUSIONS:Although cancer mortality involving ICH declined modestly over the study period, substantial disparities persist. These findings highlight the need to integrate cerebrovascular risk assessment into cancer management and survivorship care, particularly for high-risk populations and cancer subtypes.

Glioblastoma (GBM) is the most serious and most common brain tumor in humans. Despite recent advances in the diagnosis of GBM and the development of new treatments, the prognosis of patients has not improved. Multidrug resistance, particularly resistance to temozolomide (TMZ), is a challenge in combating glioma, and more effective therapies are needed. Complementary treatment with the LaSota strain of the naturally oncolytic Newcastle disease virus (NDV-LaSota) is an innovation. In our experiments, the combination therapy of NDV-LaSota and temozolomide (TMZ) was more effective than either treatment alone in inducing apoptosis in glioma cells. NDV can function as a tumor cell selective approach to inhibit AKT and activate AMPK. Consequently, mTOR, 4EBP1 and S6K were also suppressed. The combination therapy of NDV and TMZ also significantly extended survival in a rat xenograft tumor model. In conclusion, NDV suppress AKT signaling and enhances antitumor effects of TMZ. Our study provides one of the theoretical basis for the use of a combined therapy of TMZ and NDV, which could benefit GBM patients.

Prenylation is an important post-translational lipid modification that enhances protein hydrophobicity and regulates subcellular localization. It plays a critical role in multiple signaling pathways and metabolic processes and is closely associated with the development and progression of various diseases, particularly in tumor initiation, progression, and metastasis. However, its systemic regulatory roles and therapeutic vulnerabilities in cancer remain incompletely understood. In this review, we summarize the molecular mechanisms of protein prenylation and its biological functions, with a particular focus on its roles in tumorigenesis and tumor progression. We further discuss therapeutic strategies targeting prenylation, including both monotherapy and combination approaches. Overall, protein prenylation represents a key regulatory hub linking signal transduction, metabolic reprogramming, and tumorigenesis. Future studies should focus on elucidating the mechanisms underlying therapeutic response and resistance, as well as advancing clinical translation through biomarker development and well-designed clinical trials.

OBJECTIVE:High-grade glioma (HGG) is one of the most lethal malignancies. Immune escape is considered to be a reason for the failure of immunotherapy for HGG patients, and there is currently no immune escape-related prognostic model for glioma. Therefore, we explored the relationship between immune escape-related genes and the prognosis of patients with HGG. METHODS:This study combined 101 machine learning algorithms to determine the best immune escape-related prognostic model. Subsequently, the TCGA and CGGA cohorts were used to verify the effectiveness of the model. Subsequently, molecular docking, Mendelian randomization and other comprehensive analyses were performed on the model genes. Finally, the biology function of the signature gene was further verified via CCK-8, and colony formation. RESULTS:Our differential expression analysis found that 41 immune escape-related genes were significantly related to the prognosis of HGG patients. We further selected 18 key genes through various machine learning methods to construct an immune escape-related prognosis model. This model can effectively distinguish between high-risk and low-risk groups, and shows good prediction results in both CGGA and TCGA data sets. Subsequently, the risk score was found to be an independent prognostic factor, and the nomogram including clinical characteristics was constructed. Immunotherapy response prediction results show that patients in the low-risk group respond better to immunotherapy and have longer survival. Furthermore, TAB1 knockdown reduced the ability of human glioma cells to proliferate and clone. CONCLUSION:This study constructed a prognostic model related to immune escape through multiple machine learning methods and verified its clinical application value in HGG patients. It provides a theoretical basis for the exploration of immune escape treatment targets.

The Quaking protein (QKI) belongs to the STAR protein family and plays a significant role in the development of the nervous system. It serves as a crucial regulator in the processes of tumor progression and cardiovascular system development. Within the central nervous system, QKI has been associated with the onset and progression of numerous neuropsychiatric disorders, including schizophrenia, depression, ataxia, and Alzheimer’s disease. In malignant tumors, the methylation of the QKI promoter inhibits its expression. QKI primarily involves in the generation, stability, and selective splicing of non-coding RNA, as well as in mRNA translation. The role of QKI in the tumor microenvironment should not be overlooked. Especially in Glioblastoma Multiforme (GBM), although QKI is not the primary mutation, it still plays a vital role in maintaining the stemness of GBM. However, the mechanisms and further studies on this topic demand extensive basic and clinical trials.

AbstractThe emergence of programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) immunosuppressants provides new therapeutic directions for various advanced malignant cancers. At present, PD-1/PD-L1 immunosuppressants have made significant progress in clinical trials of some gliomas, but PD-1/PD-L1 inhibitors have not yet shown convincing clinical efficacy in gliomas. This article summarizes the research progress of the PD-1 /PD-L1 pathway in gliomas through the following three aspects. It mainly includes the complex expression levels and regulatory mechanisms of PD-1/PD-L1 in the glioma microenvironment, the immune infiltration in glioma immunosuppressive microenvironment, and research progress on the application of PD-1/PD-L1 immunosuppressants in clinical treatment trials for gliomas. This will help to understand the current treatment progress and future research directions better.

Our research investigated the effects of hsa-miR-134-5p on glioma progression, focusing on its interaction with the BDNF/ERK signaling pathway. U251 and U87 cell lines were analyzed post-transfection with hsa-miR-134-5p mimics and inhibitors, confirming the miRNA's binding to BDNF using dual luciferase assays. Q-PCR was employed to measure expression changes, revealing that hsa-miR-134-5p markedly inhibited glioma cell proliferation, migration, and invasion, as evidenced by CCK8, monoclonal formation, and Transwell assays. Scratch tests and Western blotting demonstrated hsa-miR-134-5p's modulation of the BDNF/ERK pathway and associated decrease in MMP2/9 protein levels. Flow cytometry suggested that hsa-miR-134-5p might also block the G0/S phase transition. In vivo studies using nude mice corroborated the tumor-suppressing effects of hsa-miR-134-5p, which were negated by elevated BDNF levels. Comparative protein analysis across groups confirmed the pathway's significance in tumorigenesis. Our findings identify hsa-miR-134-5p as a key molecule impeding glioma cell growth by curtailing the BDNF/ERK pathway, with the reversal by BDNF upregulation pointing to the potential of therapeutically exploiting the hsa-miR-134-5p/BDNF axis in glioma care.

Tumor treating fields (TTFields) therapy is a novel and effective noninvasive cancer therapy, and it has been approved by FDA in the treatment of recurrent and newly diagnosed glioblastoma, and malignant pleural mesothelioma. Moreover, TTFields therapy has been widely studied in both clinical trials and preclinical studies in recent years. Based on its high efficacy, research on TTFields therapy has been a hot topic. Thus, the authors made this scientometric analysis of TTfields to reveal the scientometric distributions such as annual publications and citations, countries and institutions, authors, journals, references, and more importantly, research status and hot topics of the field. In recent years, publication numbers have been stable at high values, and citation numbers have been increasing greatly. The United States and Israel were the top two countries with the highest publication numbers, followed by Germany and Switzerland. Scientometric analyses of keywords indicated that clinical applications and antitumor mechanisms are probably the two main parts of current research on TTfields. Most clinical trials of TTfields focus on the treatment of glioblastoma. And a variety of other cancers such as lung cancer especially nonsmall cell lung cancer, hepatic cancer, other brain tumors, etc. have also been studied in both clinical trials and preclinical studies.

Glioblastoma (GBM) is a common primary malignant brain tumor and the prognosis of these patients remains poor. Therefore, further understanding of cell cycle-related molecular mechanisms of GBM and identification of appropriate prognostic markers and therapeutic targets are key research imperatives. Based on RNA-seq expression datasets from The Cancer Genome Atlas database, prognosis-related biological processes in GBM were screened out. Gene Set Variation Analysis (GSVA), LASSO-COX, univariate and multivariate Cox regression analyses, Kaplan-Meier survival analysis, and Pearson correlation analysis were performed for constructing a predictive prognostic model. A total of 58 cell cycle-related genes were identified by GSVA and analysis of differential expression between GBM and control samples. By univariate Cox and LASSO regression analyses, 8 genes were identified as prognostic biomarkers in GBM. A nomogram with superior performance to predict the survival of GBM patients was established regarding risk score, cancer status, recurrence type, and mRNAsi. This study revealed the prognostic value of cell cycle-related genes in GBM. In addition, we constructed a reliable model for predicting the prognosis of GBM patients. Our findings reinforce the relationship between cell cycle and GBM and may help improve the prognostic assessment of patients with GBM. Our predictive prognostic model, based on independent prognostic factors, enables tailored treatment strategies for GBM patients. It is particularly useful for subgroups with uncertain prognosis or treatment challenges.

BACKGROUND:Deep vein thrombosis (DVT) of the lower extremity is one of the most common postoperative complications, especially after craniocerebral surgery. DVT may lead to pulmonary embolism, which has a devastating impact on patient prognosis. This study aimed to investigate the incidence and risk factors of DVT in the lower limbs following craniocerebral surgery.AIM:To identify independent risk factors for the development of postoperative DVT and to develop an effective risk prediction model.METHODS:The demographic and clinical data of 283 patients who underwent craniocerebral surgery between December 2021 and December 2022 were retrospectively analyzed. The independent risk factors for lower extremity DVT were identified by univariate and multivariate analyses. A nomogram was created to predict the likelihood of lower extremity DVT in patients who had undergone craniocerebral surgery. The efficacy of the prediction model was determined by receiver operating characteristic curve using the probability of lower extremity DVT for each sample.RESULTS:Among all patients included in the analysis, 47.7% developed lower extremity DVT following craniocerebral surgery. The risk of postoperative DVT was higher in those with a longer operative time, and patients with intraoperative intermittent pneumatic compression were less likely to develop postoperative DVT.CONCLUSION:The incidence of lower extremity DVT following craniocerebral surgery is significant, highlighting the importance of identifying independent risk factors. Interventions such as the use of intermittent pneumatic compression during surgery may prevent the formation of postoperative DVT.

Gliomas, originating from glial cells within the brain or spinal cord, are common central nervous system tumors with varying degrees of malignancy that influence the complexity and difficulty of treatment. The current strategies, including traditional surgery, radiotherapy, chemotherapy, and emerging immunotherapies, have yielded limited results. As such, our study aims to optimize risk stratification for a more precise treatment approach. We primarily identify feature genes associated with poor immune cell infiltration patterns through various omics algorithms and categorize glioma patients based on these genes to enhance the accuracy of patient prognosis assessment. This approach can underpin individualized treatment strategies and facilitate the discovery of new therapeutic targets. We procured datasets of gliomas and normal brain tissues from TCGA, CGGA, and GTEx databases. Clustering was conducted using the input of 287 immune cell feature genes. Hub genes linked with the poor prognosis subtype (C1) were filtered through WGCNA. The TCGA dataset served as the discovery cohort and the CGGA dataset as the external validation cohort. We constructed a prognostic model related to feature genes from poor immune cell infiltration patterns utilizing LASSO-Cox regression. Comprehensive analyses of genomic heterogeneity, tumor stemness, pathway relevance, immune infiltration patterns, treatment response, and potential drugs were conducted for different risk groups. Gene expression validation was performed using immunohistochemistry (IHC) on 98 glioma samples and 11 normal brain tissue samples. Using the filtered immune cell-related genes, glioma patients were stratified into C1 and C2 subtypes through clustering. The C1 subtype exhibited a worse prognosis, with upregulated genes primarily enriched in immune response, extracellular matrix, etc., and downregulated genes predominantly enriched in neural signal transduction and neural pathway-related aspects. Seven advanced algorithms were used to elucidate immune cell infiltration patterns of different subtypes. In addition, WGCNA identified hub genes from poor immune infiltration patterns, and a prognostic model was constructed accordingly. High-risk patients demonstrated shorter survival times and higher risk scores as compared to low-risk patients. Multivariate Cox regression analysis revealed that, after adjusting for confounding clinical factors, risk score was a vital independent predictor of overall survival (OS) (P < 0.001). The established nomogram, which combined risk scores with WHO grade and age, accurately predicted glioma patient survival rates at 1, 3, and 5 years, with AUCs of 0.908, 0.890, and 0.812, respectively. This risk score enhanced the nomogram's reliability and informed clinical decision-making. We also comprehensively analyzed genomic heterogeneity, tumor stemness, pathway relevance, immune infiltration patterns, treatment response, and potential drugs for different risk groups. In addition, we conducted preliminary validation of the potential PLSCR1 gene using IHC with a large sample of gliomas and normal brain tissues. Our optimized risk stratification strategy for glioma patients has the potential to improve the accuracy of prognosis assessment. The findings from our omics research not only enhance the understanding of the functions of feature genes related to poor immune cell infiltration patterns but also offer valuable insights for the study of glioma prognostic biomarkers and the development of individualized treatment strategies.

BackgroundUnderstanding the epidemiology and prognostic factors of low-grade gliomas (LGGs) can help estimate the public health impact and optimize risk stratification and treatment strategies.Methods3 337 patients diagnosed with LGGs were collected from the Surveillance, Epidemiology, and End Results (SEER) dataset, 2004–2019. The incidence trends of LGGs were analyzed by patient demographics (sex, age, race, and ethnicity). In addition, a competing risk regression model was used to explore the prognostic factors of LGGs by patient demographics, tumor characteristics (histological subtypes, invasiveness, and size), treatment modality, and molecular markers (IDH mutation and 1p/19q codeletion).ResultsLGGs occurred more frequently in male, non-Hispanic, and White populations. The incidence rate of mixed gliomas was stable from 2004 to 2013 and decreased dramatically to nearly zero until 2019. The risk of death increased 1.99 times for every 20-year increase in patient age, and 60 years is a predictive cut-off age for risk stratification of LGGs. Male patients showed poorer LGG-specific survival. Among the different subtypes, astrocytoma has the worst prognosis, followed by mixed glioma and oligodendroglioma. Tumors with larger size (≥5 cm) and invasive behavior tended to have poorer survival. Patients who underwent gross total resection had better survival rates than those who underwent subtotal resection. Among the different treatment modalities, surgery alone had the best survival, followed by surgery + radiotherapy + chemotherapy, but chemotherapy alone had a higher death risk than no treatment. Furthermore, age, invasiveness, and molecular markers were the most robust prognostic factors.ConclusionThis study reviewed the incidence trends and identified several prognostic factors that help clinicians identify high-risk patients and determine the need for postoperative treatment according to guidelines.

1 病例资料 30岁男性,因右眼视物模糊3个月余入院.入院体格检查未发现神经系统阳性体征;视力检查右眼0.8,左眼1.0,双侧眼压正常.头部MRI平扫及增强(图1A～E):右侧视神经管内段内上方见类圆形等T1、短T2 信号,大小约14 mm×15 mm×12 mm,其内见小类圆形长T2信号,增强后明显不均匀强化.头部CT平扫(图1F):蝶鞍右上方可见一类圆形高密度影,约1 cm,与颅前窝底骨质及右侧视神经管内上壁分界不清.术前诊断为颅内占位性病变,考虑脑膜瘤可能性大.取右侧额颞部马蹄形切口,打开骨窗后磨除部分蝶骨嵴,弧形剪开硬脑膜,轻推额叶即可见肿瘤组织.术中显示肿瘤起源于颅底骨质,骨组织有破坏,与硬脑膜关系密切,挤压视神经管但未突破硬脑膜.术中切除黄褐色沙砾样组织,大小约1.3 cm×1 cm×0.3 cm,质地韧,血运一般.术后病理检查示肿瘤细胞胞浆丰富、粉染,产生骨样基质和软骨样基质,伴陈旧性出血及多核巨细胞反应,肿瘤局部侵袭周围骨组织,诊断为软骨母细胞瘤.术后4d查头部MRI增强(图1G～I)可见肿瘤被完整切除.术后1年复查头部增强MRI示术区恢复良好,未见肿瘤复发.

Background:The incidence of meningioma is disparate to sex: meningiomas are more common in women than in men, especially in middle-aged women. Understanding the epidemiology and survival of middle-aged women with meningiomas would help estimate their public health impacts and optimize risk stratification. Methods:Data on middle-aged (35-54 years) female patients with meningiomas between 2004 and 2018 were obtained from the SEER database. Age-adjusted incidence rates per 100 000 population-years were calculated. Kaplan-Meier and multivariate Cox proportional hazard models were utilized in the overall survival (OS) analysis. Results:Data from 18302 female patients with meningioma were analyzed. The distribution of patients increased with age. Most patients were White and non-Hispanic, according to race and ethnicity, respectively. Over the past 15 years, non-malignant meningiomas have shown an increasing trend; however, malignant meningiomas have shown an opposite trend. Older age, Black population, and large non-malignant meningiomas tend to have worse prognoses. Surgical resection improves OS, and the extent of resection is a critical prognostic factor. Conclusions:This study observed an increase in non-malignant meningiomas and a decrease in the incidence of malignant meningiomas in middle-aged females. The prognosis deteriorated with age, in Black people, and with large tumor size. Additionally, the extent of tumor excision was found to be a significant prognostic factor.

Glioma, the predominant form of central nervous system (CNS) malignancies, presents a significant challenge due to its high prevalence and low 5-year survival rate. The efficacy of current treatment methods is limited by the presence of the blood-brain barrier, the immunosuppressive microenvironment, and other factors. Immunotherapy has emerged as a promising approach, as it can overcome the blood-brain barrier. A tumor's immune privilege, which is induced by an immunosuppressive environment, constricts immunotherapy's clinical impact in glioma. Pyroptosis, a programmed cell death mechanism facilitated by gasdermins, plays a significant role in the management of glioma. Its ability to initiate and regulate tumor occurrence, progression, and metastasis is well-established. However, it is crucial to note that uncontrolled or excessive cell death can result in tissue damage, acute inflammation, and cytokine release syndrome, thereby potentially promoting tumor advancement or recurrence. This paper aims to elucidate the molecular pathways involved in pyroptosis and subsequently discuss its induction in cancer therapy. In addition, the current treatment methods of glioma and the use of pyroptosis in these treatments are introduced. It is hoped to provide more ideas for the treatment of glioma.

The S protein of SARS-CoV-2 is a crucial structural and functional component for virus entry. Due to the constant mutation of the virus, there are very limited ways to prevent and control COVID-19. This experiment used a macroscopic SDS-PAGE method and proved that the S protein of wild-type SARS-CoV-2 virus, especially the S1 subunit, is very sensitive to alkaline serine protease with acidic pI (ASPNJ), NJ represents Neanthes japonica (Izuka) from which ASP is purified). ASPNJ cleaves proteins when the carbonyl group of the peptide bond is contributed by arginine or lysine. ASPNJ can degrade the S protein very quickly and effectively in vitro with relative selectivity. It can be inferred that the S, S1 and RBD of SARS-CoV-2 variants can also be easily degraded by ASPNJ. This rapid and strong degradation of the S protein by ASPNJ may become a potential new treatment strategy.

Background:Yolk sac tumor is a type of germ cell tumor. It commonly arises in the gonads but sometimes can occur outside the gonads. Primary intracranial yolk sac tumors were very rare. It is always located in the pineal, suprasellar and posterior third ventricular region. The incidence of yolk sac tumor is estimated as less than 8% of all primary intracranial germ cell tumors. Multifocal primary intracranial yolk sac tumors have seldom been reported.Case Description:Here we reported a 29 years old male patient with a sudden coma and a history of headaches for one month. Computed Tomography and magnetic resonance imaging of the head showed three masses located at the suprasellar region, pineal region and left temporal lobe separately. The mass at the left temporal lobe was successfully resected with emergency surgery, and decompressive craniectomy was also performed. Intraoperative findings revealed that the tumor was a solid mass with intra-tumoral haemorrhage. The pathology examination confirmed the diagnosis of yolk sac tumor. Hematoxylin and eosin staining clearly showed the Schiller-Duval body. Whole-brain radiotherapy was performed after the operation, and the patient died in a local hospital 11 months after the surgery.Conclusions:We reported a case of multifocal primary intracranial yolk sac tumor in an adult patient. Then we reviewed the literature and discussed the treatment and diagnosis of patients with primary intracranial yolk sac tumors.

BackgroundEpithelial–mesenchymal transition (EMT) is a key factor in the invasion and migration of glioma cells, and the study of EMT in gliomas has become a hot topic over the past decade. Scientometric analysis is gaining more attention since it can obtain hot topics and emerging trends in a research field. This article analyzed the research related to EMT in gliomas for the first time, including descriptions of research situations, evaluations of research foci, and predictions of emerging trends.MethodsWe searched the topic-related original articles from January 2012 to December 2021 in the Web of Science Core Collection (WoSCC) by using a specific strategy, and a total of 1,217 publications were obtained. The WoS platform, VOS viewer, and CiteSpace were used to analyze the annual distribution of publications and citations, authors and density of keywords, and other analyses including countries, institutions, references, clustering, burst analysis, and the timeline view of keywords.ResultsScientometric analysis identified that the study of EMT in gliomas has developed fast and received continuous attention in the last decade. Based on the results of data analysis, most publications on the topic came from China, and the United States had the highest betweenness centrality. The top 10 co-cited references revealed the landmark documents that had greatly promoted the development of this field. The major focus is on the cellular and molecular mechanisms of EMT in gliomas, and the therapy related to EMT target and non-coding RNAs has been developing fast in recent years.ConclusionsThis study revealed the intimate connections between EMT and gliomas, and the complex mechanisms regulating EMT in gliomas had been studied widely in the last decade. Exploring the deep mechanisms of EMT in gliomas is the foundation of the targeted inhibitions, which can promote the development of therapies for gliomas.

Backgrounds:TP53 germline mutation is well known to be the cause of Li-Fraumeni syndrome (LFS), a rare autosomal dominant cancer syndrome, characterized by predisposition of breast cancer, soft tissue carcinoma, osteosarcoma, brain cancer and etc. LFS has been reported in cases or small-scale cohorts for decades, while the characteristics of TP53 germline mutations carried by glioma patients were still less studied due to rarity. We performed large-scale retrospective research to identify TP53 germline mutations in Chinese glioma patients, which would extend the genetic knowledge of LFS related glioma. Methods:We enrolled 3325 glioma patients in this study (female=1423, male=1902). Next-generation sequencing panel targeting 825 genes was performed to identify TP53 germline mutations. Mutations were annotated pathogenic or likely pathogenic according to ACMG guidelines or referring to the literatures. Results:After annotation, 20 pathogenic or likely pathogenic germline mutations (PGMs) in TP53 were found in 3325 glioma patients. There was no statistical significance of gender ratio between all glioma patients and mutation carriers (female=6, male=14, p=0.25). The highest incidence rate of PGMs occurred in glioblastoma (n=16, 80.0%), followed by anaplastic astrocytoma (n=2, 10.0%), oligodendroglioma (n=1, 0.5%) and diffuse midline glioma (n=1, 0.5%). Significant difference of onset age between TP53 mutation carriers and non-carriers was pronounced (22.90YO vs 43.35YO avg, p<0.0001). Furthermore, the carrier rate of PGMs was prone to decrease with increasing onset age (table 1). Conclusions:This research indicated that TP53 PGMs were prone to occur in younger glioma patients, suggesting the importance of TP53 germline mutations being screened. It might be able to assist with early detection and treatment of glioma. The carrier rate of TP53 PGMs in each onset age intervals onset age glioma patient number PGM carrier number carrier rate 0-18 444 10 2.25% 19-30 263 4 1.52% 31-45 826 4 0.48% 46-55 717 1 0.14% 56-65 687 1 0.15% 66-75 337 0 0.00% 76+ 51 0 0.00% Citation Format: Xinyu Hong, Ximeng Zhao, Zeshang Guo, Xiaochen Yang, Bella Guo, Xiang Zhang, Tonghui Ma. The characteristics of TP53 germline mutations analyzed in a large-scale cohort of Chinese glioma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5840.

Abstract Purpose The present study aimed to identify the role of long non-coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) in the progression of glioblastoma multiforme (GBM) and the regulatory mechanism of the SNHG1/miR-128-3p/RRAS2 network. Methods The TargetScan method was used to analyze the target mRNAs and associated miRNAs of SNHG1. The levels of SNHG1, miRNAs, and mRNAs were determined in glioma and normal brain tissues based on The Cancer Genome Atlas. Pathway analysis was used to identify the significant pathways of the predicted target genes of SNHG1 according to the Kyoto Encyclopedia of Genes and Genomes. The expressions of SNHG1 in GBM cells were determined by real-time quantitative polymerase chain reaction (qRT-PCR). A scratch wound-healing and Transwell assays were used to determine GBM cell migration and invasion. The dual-luciferase reporter assay was used to validate the miR-128-3p target relationships with lncRNA SNHG1. Western blotting was performed to determine whether SNHG1 and RRAS2 regulated the epithelial-mesenchymal transition (EMT) process of GBM cells. Results SNHG1 was upregulated in glioma tissues and cells. Knockdown of SNHG1 inhibited migration and invasion of GBM cells. A competing endogenous RNA interaction network of SNHG1-6miRNAs-17mRNAs was constructed and revealed the functional role of the SNHG1/miR-128-3p/RRAS2 feed-forward loop. MiR-128-3p expression was downregulated in glioma tissues, whereas RRAS2 expression was elevated in glioma tissues. QRT-PCR and dual luciferase reporter analyses of the results indicated that SNHG1 bound to miR-128-3p, while SNHG1 expression was negatively regulated by miR-128-3p. Additionally, miR-128-3p regulated the expression of RRAS2 mRNA. Moreover, knockdown of RRAS2 inhibited GBM cell migration and invasion. Collectively, SNHG1 promoted GBM progression by sponging miR-128-3p and regulating RRAS2 expression. In addition, down-regulations of SNHG1 and RRAS2 significantly reduced the expressions of mesenchymal markers, N-cadherin and vimentin, while it increased the protein level of E-cadherin epithelial marker, showing that silencing SNHG1 reversed the EMT phenotype. Conclusion Our findings confirmed that lncRNA SNHG1 promoted the malignant progression of GBM by the SNHG1/miR-128-3p/RRAS2 axis, which activated the EMT process. The SNHG1/miR-128-3p/RRAS2 axis therefore may provide a novel therapeutic treatment for GBM.