LINC01393, a Novel Long Non-Coding RNA, Promotes the Cell Proliferation, Migration and Invasion through MiR-128-3p/NUSAP1 Axis in Glioblastoma.

Nucleolar and spindle-associated protein 1 (NUSAP1) is a potential molecular marker and intervention target for glioblastoma (GBM). In this study, we aim to investigate upstream regulatory lncRNAs and miRNAs of NUSAP1 through both experimental and bioinformatic methods. We screened upstream lncRNAs and miRNAs of NUSAP1 through multiple databases based on ceRNA theory. Then, in vitro and in vivo experiments were performed to elucidate the relevant biological significance and regulatory mechanism among them. Finally, the potential downstream mechanism was discussed. LINC01393 and miR-128-3p were screened as upstream regulatory molecules of NUSAP1 by TCGA and ENCORI databases. The negative correlations among them were confirmed in clinical specimens. Biochemical studies revealed that overexpression or knockdown of LINC01393 respectively enhanced or inhibited malignant phenotype of GBM cells. MiR-128-3p inhibitor reversed LINC01393 knockdown-mediated impacts on GBM cells. Then, dual-luciferase reporter assay and RNA immunoprecipitation assay were conducted to validate LINC01393/miR-128-3p/NUSAP1 interactions. In vivo, LINC01393-knockdown decreased tumor growth and improved mice survival, while restoration of NUSAP1 partially reversed these effects. Additionally, enrichment analysis and western blot revealed that the roles of LINC01393 and NUSAP1 in GBM progression were associated with NF-κB activation. Our findings showed that LINC01393 sponged miR-128-3p to upregulate NUSAP1, thereby promoting GBM development and progression via activating NF-κB pathway. This work deepens understanding of GBM mechanisms and provides potential novel therapeutic targets for GBM.

Prognosis and Immunological Characteristics of PGK1 in Lung Adenocarcinoma: A Systematic Analysis.

Background: Aerobic glycolysis plays a key role in tumor metabolic reprogramming to reshape the immune microenvironment. The phosphoglycerate kinase 1 (PGK1) gene codes a glycolytic enzyme that converts 1,3-diphosphoglycerate to 3-phosphoglycerate. However, in lung adenocarcinoma (LUAD), the role of PGK1 in altering the tumor microenvironment (TME) has not yet been determined. Methods: Raw data, including bulk DNA and mRNA-seq data, methylation modification data, single-cell RNA-seq data, proteomics data, clinical case characteristics survival, immunotherapy data, and so on, were obtained from multiple independent public data sets. These data were reanalyzed to uncover the prognosis and immunological characteristics of PGK1 in LUAD. Results: We found that PGK1 mRNA and protein were considerably over-expressed in LUAD compared to normal tissue and that high PGK1 expression is associated with poorer prognostic outcomes in LUAD. The enrichment analysis of PGK1 co-expressed genes in lung adenocarcinoma revealed that PGK1 may be involved in hypoxia, metabolism, DNA synthesis, cell cycle, PI3K/AKT, and various immune and inflammatory signaling pathways. Furthermore, PGK1 is also linked to the recruitment of numerous immune cells, including aDC (dendritic cells), macrophages, and neutrophils. More importantly, PGK1 was highly expressed in immunosuppressive cells, including M2 macrophages, Tregs, and exhausted T cells, among others. Finally, higher PGK1 expression indicated significant correlations to immune checkpoints, TMB (tumor mutation burden), and high response to immunotherapy. Conclusions: The presented findings imply that PGK1, as a glycolysis core gene, may be important for the modification of the immune microenvironment by interacting with the tumor metabolism. The results of this study provide clues for a potential immunometabolic combination therapy strategy in LUAD, for which more experimental and clinical translational research is needed.

Secreted phosphoprotein 1 promotes angiogenesis of glioblastoma through upregulating PSMA expression via transcription factor HIF1α.

Glioblastoma multiforme (GBM) is a highly vascularized malignant brain tumor. Our previous study showed that prostate-specific membrane antigen (PSMA) promotes angiogenesis of GBM. However, the specific mechanism underlying GBM-induced PSMA upregulation remains unclear. In this study, we demonstrate that the GBM-secreted cytokine phosphoprotein 1 (SPP1) can regulate the expression of PSMA in human umbilical vein endothelial cells (HUVECs). Our mechanistic study further reveals that SPP1 regulates the expression of PSMA through the transcription factor HIF1α. Moreover, SPP1 promotes HUVEC migration and tube formation. In addition, HIF1α knockdown reduces the expression of PSMA in HUVECs and blocks the ability of SPP1 to promote HUVEC migration and tube formation. We further confirm that SPP1 is abundantly expressed in GBM, is associated with poor prognosis, and has high clinical diagnostic value with considerable sensitivity and specificity. Collectively, our findings identify that the GBM-secreted cytokine SPP1 upregulates PSMA expression in endothelial cells via the transcription factor HIF1α, providing insight into the angiogenic process and promising candidates for targeted GBM therapy.

An integrated pan-cancer analysis of PSAT1: A potential biomarker for survival and immunotherapy.

Phosphoserine aminotransferase 1 (PSAT1) may be an oncogene that plays an important role in various cancer types. However, there are still many gaps in the expression of PSAT1 gene and its biological impact in different types of tumors. Here, we performed an integrated pan-cancer analysis to explore the potential molecular mechanisms of PSAT1 in cancers. We found that most human tumors express higher levels of PSAT1 than normal tissues, and that higher PSAT1 expression is associated with worse prognosis in Lung adenocarcinoma (LUAD), Pan-kidney cohort (KIPAN) and breast invasive carcinoma (BRCA), etc. In BRCA cases, the prognosis of patients with altered PSAT1 was worse than that of patients without alteration. In addition, PSAT1 hypermethylation is associated with T cell dysfunction and shortened survival time in BRCA. The Gene Set Enrichment Analysis (GSEA) analysis showed that PSAT1 can be enriched into the classic signaling pathways of cancer such as mTORC1 signaling, MYC targets and JAK STAT3. Further analysis demonstrated that PSAT1 was enriched in immune related signaling pathways in LUAD and BRCA. The results of immunoassay showed that PSAT1 was associated with immune cell infiltration in multiple cancer species. Furthermore, expression of PSAT1 was correlated with both tumor mutational burden (TMB) and microsatellite instability (MSI) in BRCA. Additionally, a remarkable correlation was found between PSAT1 expression and TMB in LUAD, and the expression of PSAT1 was negatively correlated with the Tumor Immune Dysfunction and Exclusion (TIDE) value, suggesting a good effect of immunotherapy. Together, these data suggest that PSAT1 expression is associated with the clinical prognosis, DNA methylation, gene mutations, and immune cell infiltration, contributing to clarify the role of PSAT1 in tumorigenesis from a variety of perspectives. What's more, PSAT1 may be a new biomarker for survival and predicting the efficacy of immunotherapy for LUAD and BRCA.

Preoperative neutrophil-to-lymphocyte ratio (preNLR) for the assessment of tumor characteristics in lung adenocarcinoma patients with brain metastasis.

OBJECTIVES: Brain metastases from lung adenocarcinoma cause significant patient mortality. This study aims to evaluate the role of preoperative Neutrophil-to-Lymphocyte ratio (preNLR) in predicting the survival and prognosis of Lung adenocarcinoma (LUAD) patients with brain metastasis (BM) and provide more references for predicting peritumoral edema. METHODS: We retrospectively reviewed 125 LUAD-BM patients who had undergone surgical resection from December 2015 to December 2020. The clinical characteristic, demographic, MRI data, and preNLR within 24-48 h before craniotomy were collected. Patients were divided into two groups based on preNLR (high NLR and low NLR), with cutoff values determined by receiver operating characteristic (ROC) analysis. Association between preoperative NLR and clinical features was determined by using Pearson chi-squared tests. Uni- and multivariate analyzes were performed to compare the overall survival (OS) of clinical features. RESULTS: The patients were divided into NLR-low (64 patients) and NLR-high (61 patients) groups based on receiver operating characteristic analysis of NLR area. According to correlation analysis, a high preNLR (NLR≥2.8) is associated with the both supra- and infratentorial location involved (P = 0.017) and a greater incidence of severe peritumoral edema (P = 0.038). By multivariable analysis, age ≥ 65 years (P = 0.011), KPS < 70 (P = 0.043), elevated preNLR (P = 0.013), extracerebral metastases (P = 0.003), EGFR/ALK+ (P = 0.037), postoperative radiotherapy (P = 0.017) and targeted therapy (P = 0.007) were independent prognostic factors. OS nomogram was constructed based on cox model and model performance was examined (AUC = 0.935). CONCLUSIONS: PreNLR may serve as a prognosis indicator in LUAD patients with brain metastasis, and high preNLR tends to be positively associate with multiple locations and severe peritumoral edema.

Transcriptome analysis of L-leucine-producing Corynebacterium glutamicum under the addition of trimethylglycine.

It has been widely reported that the addition of trimethylglycine (betaine) decreases osmotic pressure inhibition for cell growth, leading to increased production of amino acids. However, the underlying mechanism is unclear. To determine the global metabolic differences that occur under the addition of trimethylglycine, transcriptome analysis was performed. Transcriptome analysis of Corynebacterium glutamicum JL1211 revealed that 272 genes exhibited significant changes under trimethylglycine addition. We performed Gene Ontology (GO) and KEGG enrichment pathway analyses on these differentially expressed genes (DEGs). Significantly upregulated genes were mainly involved in the regulation of ABC transporters, especially phosphate transporters and sulfur metabolism. The three phosphate transporter genes pstC, pstA and pstB were upregulated by 13.06-fold, 29.80-fold and 30.49-fold, respectively. Notably, the transcriptional levels of the cysD, cysN, cysH and sir genes were upregulated by 81.5-fold, 57.3-fold, 77.6-fold and 125.4-fold, respectively, consistent with assimilatory sulfate reduction under the addition of trimethylglycine. The upregulation of ilvBN and leuD genes might result in increased L-leucine formation. The data indicated changes in the transcriptome of C. glutamicum with trimethylglycine treatment, thus providing a mechanism supporting the application of trimethylglycine in the production of L-leucine and other amino acids by C. glutamicum strains.

Systematic Analysis Uncovers Associations of PGK1 with Prognosis and Immunological Characteristics in Breast Cancer.

OBJECTIVE: Phosphoglycerate kinase 1 (PGK1) is an essential enzyme in the process of glycolysis and mitochondrial metabolism. Herein, we conducted a systematic analysis to uncover the clinical implication of PGK1 deregulation in breast cancer. METHODS: Expression pattern and prognostic significance of PGK1 were comprehensively assessed across pan-cancer based on RNA-seq profiles from the TCGA project. Associations of PGK1 with immunological features in the tumor microenvironment (immune checkpoints, immune response predictors (tumor mutation burden (TMB) and microsatellite instability (MSI)), and tumor-infiltrating immune cells) were systematically analyzed. The role of PGK1 in the prediction of breast cancer prognosis was also evaluated. GSEA was presented for investigating biological pathways involved in PGK1. RESULTS: PGK1 was specifically overexpressed in most of cancer types, including breast cancer. High PGK1 expression was indicative of undesirable overall survival, progression-free interval, disease-specific survival, and disease-free interval for various cancers. Furthermore, high PGK1 levels exhibited prominent correlations to immune checkpoints and high response to immunotherapy across pan-cancer. Notably, ROC curves confirmed that PGK1 can robustly predict breast cancer prognosis. Furthermore, PGK1 might shape an inflamed tumor microenvironment following the evidence that PGK1 was positively correlated to the abundance levels of tumor-infiltrating immune cells such as CD8+ T cell and NK cell in breast cancer. GSEA results revealed that PGK1 participated in metabolism and carcinogenic pathways. CONCLUSION: Collectively, PGK1 was capable of robustly predicting the prognosis and response to cancer immunotherapy in breast cancer.

Circular RNA SERPINE2 promotes development of glioblastoma by regulating the miR-361-3p/miR-324-5p/BCL2 signaling pathway.

Circular RNA (circRNA) is a new type of long-sequence RNA formed by a noncanonical form of alternative splicing called back-splicing. Emerging evidence has revealed that circRNAs are involved in cancer progression, regulating cancer-related genes through sponging microRNAs (miRNAs). In our study, we identified a novel upregulated circRNA, circSERPINE2, through analyzing circRNAs microarray data of glioblastoma from GEO datasets (GSE146463). Quantitative real-time PCR was used to further confirm the upregulation of circSERPINE2 in glioblastoma cell lines and tissues. Silencing circSERPINE2 inhibits glioblastoma proliferation in vivo and in vitro through cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry analysis, and western blot analysis and xenograft tumor model. Mechanistically, circSERPINE2 could directly sponge miR-324-5p and miR-361-3p. BCL2, known as a novel anti-apoptosis gene, is a target gene both of miR-324-5p and miR-361-3p. Thus, circSERPINE2 promotes BCL2 expression through sponging miR-324-5p and miR-361-3p. In conclusion, our study revealed the biological function and mechanism of circSERPINE2 in glioblastoma progression and that circSERPINE2 could be a potential therapeutic target for glioblastoma.

Dysregulation of lncRNA-CCRR contributes to brain metastasis of breast cancer by intercellular coupling via regulating connexin 43 expression.

Cardiac conduction regulatory RNA (CCRR) is down-regulated in the pathogenesis of heart failure (HF), which accordingly suppresses cardiac conduction while promoting arrhythmogenicity. Meanwhile, CX43 was reported to play a role in the pathogenesis of metastatic breast cancer and melanoma brain colonization. In this study, we studied the role of long non-coding RNA CCRR and its interaction with CX43 in brain metastasis of breast cancer. Breast cancer patients were grouped according to the metastasis status. Real-time PCR and IHC assay were used to measure the expression of lncRNA-CCRR and CX43 in patients. Western blot was conducted to observe the effect of lncRNA-CCRR on the expression of CX43 in MDA-MB-231BR and BT-474BR cells. Compared with the non-metastasis group, the mRNA expression of tissue lncRNA-CCRR, cerebrospinal fluid (CSF) lncRNA-CCRR, tissue CX43 and tissue protein expression of CX43 were both evidently up-regulated in metastasis patients, especially in patients with brain metastasis. The expression of lncRNA-CCRR was positively correlated with the up-regulated expression of CX43. Moreover, CX43 expression was significantly lower in MDA-MB-231WT cells compared with that in MDA-MB-231BR cells. Also, the overexpression of lncRNA-CCRR evidently increased dye transfer rate from astrocytes to MDA-MB-231BR/BT-474BR cells but reduced lncRNA-CCRR expression and suppressed the transmigration of MDA-MB-231BR/BT-474BR cells in a blood-brain barrier (BBB) model. In this study, we demonstrated that the presence of lncRNA-CCRR could up-regulate the expression of CX43, which promoted gap junction formation in brain metastasis of breast cancer. Accordingly, the communication between breast cancer cells and astrocytes was also promoted.

Exonuclease 1 (EXO1) is a Potential Prognostic Biomarker and Correlates with Immune Infiltrates in Lung Adenocarcinoma.

BACKGROUND: Exonuclease 1 (EXO1) has been identified to be highly expressed in different human malignancies, but its expression and prognostic role in lung adenocarcinoma (LUAD) remain unknown. MATERIALS AND METHODS: Two independent cohorts extracted from public databases and one cohort from our center were analyzed in this study. Expression levels of EXO1 in LUAD tissues and paired para-cancer tissues were detected. The prognostic value of EXO1 in LUAD patients was evaluated in the three cohorts. Enrichment analyses were performed to explore the possible underlying biological pathways. Moreover, we also explored the correlations between EXO1 and tumor-infiltrating immune cells and evaluated the impact of EXO1 knock-down on the migration of lung cancer cells. RESULTS: In this study, we found that EXO1 was highly expressed in LUAD tissues compared with para-cancerous tissues in public databases (p < 0.01), which was consistent with our data (p < 0.01). Survival analysis indicated that high expression of EXO1 was associated with poor prognosis in LUAD (p < 0.01). Enrichment analyses indicated that biological pathways like cell cycle regulation, DNA damage and repair, immune response, neuroactive ligand-receptor interaction, may be associated with EXO1 aberrant expression. Moreover, high expression of EXO1 was correlated with decreased infiltrating B cells (p < 0.01) and CD4+ T cells (p < 0.01) levels, and low infiltrating levels of B cells (p < 0.01) and dendritic cells (DCs) (p < 0.05) indicated poor overall survival (OS) in LUAD. Additionally, in vitro experiments suggested that knockdown of EXO1 may inhibit the migratory ability of lung cancer cells. CONCLUSION: In conclusion, EXO1 is a potential prognostic biomarker in LUAD, and correlates with infiltrating levels of immune cells in the tumor microenvironment. Further prospective validation of EXO1 in lung cancer is warranted.

Long noncoding RNA LINC00346 promotes glioma cell migration, invasion and proliferation by up-regulating ROCK1.

Long noncoding RNAs have key roles in glioma progression. However, the function and mechanisms of action of the long noncoding RNA, LINC00346, in glioma remain unclear. In our study, we observed that LINC00346 levels were increased in glioma tissue samples, and according to Gene Expression Profiling Interactive Analysis, its levels were related to disease-free survival and overall survival rates, suggesting that a high level of LINC00346 expression corresponds to a poor prognosis. We next confirmed the high levels of LINC00346 expression in glioma tissues and cell lines and showed that LINC00346 knockdown suppressed glioma cell proliferation, migration and invasion; promoted apoptosis; and delayed tumour growth. Moreover, the oncogenic function of LINC00346 may be explained, in part, by the down-regulation of miR-340-5p and the de-repression of ROCK1. We showed that LINC00346 may function as a competing endogenous RNA of miR-340-5p, thereby de-repressing ROCK1. This study revealed a new regulatory network in glioma and identified potential therapeutic targets for this cancer.

Prognostic values of SNAI family members in breast cancer patients.

BACKGROUND: Breast cancer (BC) is one of the most lethal malignant tumors and the leading cause of cancer-related death worldwide. Although early diagnostic techniques for BC have been well developed, 40% of cases are still diagnosed at the advanced stage, while for BC patients with distant metastases, the 5-year survival rate is usually lower than 30%. The Snail family, generally regarded as transcriptional repressors, has been indicated to be an essential prognostic factor in malignant tumors. However, limited data exist on public databases concerning the prognostic value of individual Snail family members in BC, especially SNAI3. METHODS: Data from public databases including cBioPortal for Cancer Genomics, Gene Expression Omnibus, UCSC Xena Browser, and Human Protein Atlas (HPA) were downloaded. Based on the Kaplan¬-Meier plotter platform, correlation of the three members of the Snail family and prognosis in BC were analyzed. Individual Snail family members and their co-expressed genes were respectively enriched on different pathways and biological processes via the functional enrichment analysis (FunRich) tool. RESULTS: High SNAI1 mRNA expression was associated with shorter distant metastasis-free survival (DMFS) in all BC patients regardless of PAM50 subtype. Conversely, high SNAI3 mRNA expression was associated with longer DMFS. Although the presence of SNAI2 expression was significantly associated with DMFS in the whole cohort, no significant correlation was found in patients with luminal A or HER2 subtype. For patients with the most diverse clinicopathological features, high SNAI1 expression was associated with poor survival, with the converse being true for SNAI3. However, the impact on prognosis of patients with different clinicopathological features produced by SNAI2 expression was inconclusive. Furthermore, we discovered that SNAI1 or SNAI2 and their co-expressed genes frequently enriched receptor tyrosine kinase (RTK) signaling and integrin-related pathways which mainly functioned on epithelial-mesenchymal transition and were further involved in several processes of signal transduction and cell communication. Furthermore, as SNAI3, along with its co-expressed genes, enriched immune-related pathways, it may thus play a role in mediating the immune system. CONCLUSIONS: Our analysis revealed that SNAI1 mRNA expression may potentially be a negative prognostic factor, whereas SNAI3 mRNA was associated with positive prognosis in BC. Therefore, the assessment of SNAI1 and SNAI3 expression may be valuable for predicting prognosis in BC patients.

Downregulation of LINC01140 is associated with adverse features of breast cancer.

Breast cancer (BC) is one of the most dangerous malignant diseases among women. A growing amount of evidence has suggested that long non-coding RNAs participate in the development and progression of BC and may potentially serve as therapeutic targets or prognostic markers for the disease. A previous study demonstrated that long intergenic non-protein coding RNA 01140 (LINC01140) was prominently correlated with overall survival in patients with gastric cancer. However, the function of LINC01140 in BC has not yet been elucidated. Therefore, the present study aimed to investigate the roles and molecular mechanisms underlying LINC01140 in BC. LINC01140 expression in 1,085 breast cancer patients and 291 healthy subjects was analyzed from the Gene Expression Profiling Interactive Analysis website. The association between LINC01140 expression and T stages, LINC01140-related biological pathways, and the correlation between LINC01140 expression genes were also analyzed in 825 patients with BC through the cBioPortal database. The present study demonstrated that LINC01140 expression was significantly decreased in the tumor samples compared with normal samples in patients with BC (P<0.05). The present study revealed that LINC01140 expression was significantly decreased in the T4 stage compared with T1, T2 or T3 stage (P<0.01). In addition, high expression levels of LINC01140 predicts longer relapse-free survival probability in patients with BC. It was also observed that LINC01140 participates in a variety of biological pathways, particularly in the epithelial-to-mesenchymal transition. The co-expression relationship between the LINC01140 and an abundance of genes in samples from the BC study was investigated. These genes, such as chordin like 1 and bone morphogenic protein 6, participate in the development and progression of tumor growth and bone metastasis. Finally, the present study observed the interaction between microRNA (miR)-200b and miR-200c with LINC011440. The results from the present study indicated that higher expression of LINC01140 was beneficial for patients with BC. LINC01140 may be a potential biomarker for the prognosis of patients with BC. The role of LINC01140 in BC needs to be further evaluated.

[Efficacy and safety of Gantaishu Capsules for viral B hepatitis:a systematic review and Meta-analysis].

To evaluate the efficacy and safety of Gantaishu Capsules in the treatment of viral B hepatitis. The randomized controlled trials( RCT) retrieved from Cochrane Library,PubMed,Sino Med,CNKI,Wan Fang and VIP were enrolled. The methodology quality of the included studies was evaluated,and a Meta-analysis was performed using Rev Man 5. 3 software. A total of six randomized controlled trials were included. Meta-analysis results showed that the similarities in the negative conversion rate of HBe Ag( RR = 2. 09,95%CI[0. 90,4. 85],P = 0. 09,I2= 0%),the HBV-DNA negative rate( RR = 1. 49,95% CI[0. 56,3. 95],P = 0. 43,I2= 0%) and the changes in ALT levels before and after treatment( RR =-6. 28,95%CI[-72. 83,60. 27],P = 0. 85,I2= 99%),with no statistical difference. In terms of quality of life,Gantaishu Capsules can significantly alleviate the symptoms of hepatitis B patients,with less adverse reactions. Gantaishu Capsules and Dongbao Gantai Tablets were similar in antiviral effect. In this term,Gantaishu Capsules was superior to Dangfei Liganning Capsules. It can significantly alleviate the symptoms of chronic hepatitis B patients,with a good clinical safety.Therefore,it can be applied in the case of syndrome differentiation and treatment. In view of the low quality of the included studies,more high-quality clinical trials were required to confirm its efficacy.

Preoperative Embolization Versus Direct Surgery of Meningiomas: A Meta-Analysis.

BACKGROUND: Preoperative embolization (POE) of meningioma has been established to facilitate surgical resection, which may reduce intraoperative blood loss and surgical time. However, no consensus has been achieved in meningioma treatment and no meta-analysis has been conducted. The purpose of this study was to perform a systematic review and meta-analysis and provide evidence of the efficacy of meningioma treatment with POE and direct surgery. METHODS: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. A systematic search was performed using PubMed and EMBASE. Meta-analysis was performed using the risk ratio of overall complication, mean difference (MD) of blood loss, and surgical time. The I2 statistic was used to assess the heterogeneity. RESULTS: Eight studies (1 randomized controlled trial and 7 non-randomized controlled trials) were included, in which 510 patients met the inclusion criteria. We found that preoperative embolization for patients with meningioma did not increase the overall complication rate (risk ratio = 0.92, 95% confidence interval [CI] 0.61-1.38) and can significantly reduce intraoperative blood loss (MD = -65.10, 95% CI -124.76 to -20.82) and surgical time (MD = -38.48, 95% CI -64.03 to -12.93) compared with the control patients. No significant publication bias was observed. CONCLUSIONS: This meta-analysis supports the hypothesis that POE of meningioma is a useful adjunct in meningioma treatment. This technique helps reduce blood loss and surgical time during meningioma resection.

LASP1 promotes glioma cell proliferation and migration and is negatively regulated by miR-377-3p.

Glioma is one of the most aggressive and lethal human cancers with a low cure rate. LASP1 plays an oncogenic role in multiple human cancers; however, its role in glioma remains largely unknown. Here, we found that LASP1 was highly expressed in glioma tissue samples. Functionally, knockdown of LASP1 significantly suppressed glioma cell proliferation and migration in vitro and tumorigenicity in vivo. These effects were found to be mechanistically associated with suppression of AKT activity. Furthermore, we identified LASP1 as a direct target of miR-377-3p. Overexpression of miR-377-3p reduced the expression of LASP1 and suppressed the proliferation and migration of glioma cells. Restoration of LASP1 expression in miR-377-3p-overexpressing cells attenuated the inhibition of glioma cell malignancy and reversed the dephosphorylation of AKT. Taken together, our results suggest that LASP1 activates the PI3K/AKT signaling pathway and is downregulated by miR-377-3p during glioma progression. These data provide a new possible therapeutic target in glioma.

Long Intergenic Noncoding RNA 00152 Promotes Glioma Cell Proliferation and Invasion by Interacting with MiR-16.

BACKGROUND/AIMS: Long noncoding RNAs (lncRNAs) are a novel class of protein-noncoding transcripts that are aberrantly expressed in multiple diseases including cancers. LINC00152 has been identified as an oncogene involved in many kinds of cancer; however, its expression pattern and function in human glioma remain unclear. METHODS: Quantitative real-time polymerase chain reaction was carried out to measure LINC00152 expression in human glioma cell lines and tissues. CCK-8 and EdU assays were performed to assess cell proliferation, and scratch assays and Transwell assays were used to assess cell migration and invasion, respectively. Luciferase reporter assays were carried out to determine the interaction between miR-16 and LINC00152. In vivo experiments were conducted to assess tumor formation. RESULTS: LINC00152 was found to be significantly upregulated in human glioma cell lines and clinical samples. Knockdown of LINC00152 suppressed glioma cell proliferation, migration, and invasion in vitro. In vivo assays in nude mice confirmed that LINC00152 knockdown inhibits tumor growth. Furthermore, mechanistic investigation showed that LINC00152 binds to miR-16 in a sequence-specific manner and suppresses its expression. miR-16 inhibition strongly attenuated LINC00152 knockdown-mediated suppressive effects on proliferation, migration, and invasion. Moreover, LINC00152 induced BMI1 expression by sponging miR-16; this effect further promoted glioma cell proliferation and invasion. CONCLUSION: We regard LINC00152 as an oncogenic lncRNA promoting glioma cell proliferation and invasion and as a potential target for human glioma treatment.

Histone deacetylase SIRT6 inhibits glioma cell growth through down-regulating NOTCH3 expression.

Gliomas are the most common brain tumors of the central nervous system. In this study, we investigated the molecular mechanisms and biological function of SIRT6 in human gliomas. The expression levels of SIRT6 in glioma tissues and cells were analyzed by qRT-PCR and western blot analysis. CCK8 and clonogenicity assays were performed to detect the cell proliferation. Furthermore, the migration and invasion of glioma cells were examined by transwell assays. It was found that the expression of SIRT6 was significantly lower in human glioma tissues or cell lines compared with the normal brain tissue or NHA. Up-regulated SIRT6 significantly decreased cell proliferation, migration and invasion of U87 and U251 cells. By contrast, knockdown of SIRT6 dramatically increased cell proliferation, migration and invasion of U87 and U251 cells. Moreover, over expression of NOTCH3 significantly increased the cell proliferation, migration, and invasion of U87 and U251 cells. However, these effects were abolished after overexpression of SIRT6. These results suggest that SIRT6 may suppress cell proliferation, migration, and invasion via inhibition of the NOTCH3 signaling pathway in glioma.

LncRNA-TP53TG1 Participated in the Stress Response Under Glucose Deprivation in Glioma.

Gliomas are the most common brain tumors of the center nervous system. And long non-coding RNAs (lncRNAs) are non-protein coding transcripts, which have been considered as one type of gene expression regulator for cancer development. In this study, we investigated the role of lncRNA-TP53TG1 in response to glucose deprivation in human gliomas. The expression levels of TP53TG1 in glioma tissues and cells were analyzed by qRT-PCR. In addition, the influence of TP53TG1 on glucose metabolism related genes at the mRNA level during both high and low glucose treatment was detected by qRT-PCR. MTT, clonogenicity assays, and flow cytometry were performed to detect the cell proliferation and cell apoptosis. Furthermore, the migration of glioma cells was examined by Transwell assays. The expression of TP53TG1 was significantly higher in human glioma tissues or cell lines compared with normal brain tissue or NHA. Moreover, TP53TG1 and some tumor glucose metabolism related genes, such as GRP78, LDHA, and IDH1 were up-regulated significantly in U87 and LN18 cells under glucose deprivation. In addition, knockdown of TP53TG1 decreased cell proliferation and migration and down-regulated GRP78 and IDH1 expression levels and up-regulated PKM2 levels in U87 cells under glucose deprivation. However, over-expression of TP53TG1 showed the opposite tendency. Moreover, the effects of TP53TG1 were more remarkable in low glucose than that in high glucose. Our data showed that TP53TG1 under glucose deprivation may promote cell proliferation and migration by influencing the expression of glucose metabolism related genes in glioma. J. Cell. Biochem. 118: 4897-4904, 2017. © 2017 Wiley Periodicals, Inc.