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Expression map of the six lncRNA signature across five glioblastoma subtypes. Kruskal-Wallis test was used to compare the expression levels for each lncRNAs across five glioblastoma subtypes

Expression map of the six lncRNA signature across five glioblastoma subtypes. Kruskal-Wallis test was used to compare the expression levels for each lncRNAs across five glioblastoma subtypes

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Recent studies have demonstrated the utility and superiority of long non-coding RNAs (lncRNAs) as novel biomarkers for cancer diagnosis, prognosis, and therapy. In the present study, the prognostic value of lncRNAs in glioblastoma multiforme was systematically investigated by performing a genome-wide analysis of lncRNA expression profiles in 419 gl...

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... Both types of GBM bear distinct genetic and epigenetic signposts and are histologically indistinguishable . Some characteristic pathophysiological features of GBM include hypoxia, necrosis, neo-angiogenesis, genetic deficiency, and poor prognosis, with an approximately 90% mortality rate (Phillips et al., 2018;Zhou et al., 2018). Ostrom et al. (2018) showed that 3.1 individuals are diagnosed with GBM per 100,000 individuals, with male populations more susceptible to this debilitating malignancy. ...
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Glioblastoma multiforme (GBM) is regarded as the most aggressive form of brain tumor delineated by high cellular heterogeneity; it is resistant to conventional therapeutic regimens. In this study, the anti-cancer potential of garcinol, a naturally derived benzophenone, was assessed against GBM. During the analysis, we observed a reduction in the viability of rat glioblastoma C6 cells at a concentration of 30 µM of the extract (p < 0.001). Exposure to garcinol also induced nuclear fragmentation and condensation, as evidenced by DAPI-stained photomicrographs of C6 cells. The dissipation of mitochondrial membrane potential in a dose-dependent fashion was linked to the activation of caspases. Furthermore, it was observed that garcinol mediated the inhibition of NF-κB (p < 0.001) and decreased the expression of genes associated with cell survival (Bcl-XL, Bcl-2, and survivin) and proliferation (cyclin D1). Moreover, garcinol showed interaction with NF-κB through some important amino acid residues, such as Pro²⁷⁵, Trp²⁵⁸, Glu²²⁵, and Gly²⁵⁹ during molecular docking analysis. Comparative analysis with positive control (temozolomide) was also performed. We found that garcinol induced apoptotic cell death via inhibiting NF-κB activity in C6 cells, thus implicating it as a plausible therapeutic agent for GBM.
... Furthermore, Huang et al. successfully constructed a signature of irlncRNAs with strong predictive function, which provided particular guidance for analyzing the pathogenesis, clinical treatment, and potential therapeutic targets of glioma [11]. Sun et al. analyzed the expression of a set of six irlncRNAs to build a signature for predicting the survival of GBM patients [12]. Zhao et al. constructed a signature involving 5 irlncRNAs to predict the prognosis of gliomas [13]. ...
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Background Despite tremendous evolution in therapies, the prognosis of glioblastoma (GBM) remains grim, which calls for innovative approaches to optimize chemotherapy efficacy and predict risk. Methods The transcriptome and clinical data of GBM were acquired from the Cancer Genome Atlas (TCGA), followed by the identification of differentially expressed immune-related long noncoding RNAs (DEirlncRNAs) with Pearson correlation and limma packet analyses. Survival-related DEirlncRNA pairs were screened with univariate Cox proportional hazard regression. Prognostic markers were obtained, and risk scores were calculated with Lasso regression and multivariate Cox risk regression analyses. The association of the prognostic risk model with immune cell infiltration was evaluated by comprehensively analyzing tumor-infiltrating immune cells with TIMER, XCELL, CIBERSORT, QUANTISEQ, and EPIC. Differences in half-maximal inhibitory concentration (IC50) values between the high- and low-risk groups were assessed with the Wilcoxon signed-rank test. Results A total of 276 DEirlncRNAs were identified, followed by the visualization of their expression patterns. Two prognosis-related DEirlncRNA pairs were screened, with high accuracy and reliability. The constructed prognostic risk model effectively distinguished between high- and low-risk patients, and significant differences were observed in survival outcomes between the high- and low-risk groups. Furthermore, risk scores were associated with tumor-infiltrating immune cells and DEirlncRNA expression. Additionally, the risk model had a correlation with the effectiveness of commonly used chemotherapeutic agents, providing clues into potential treatment responses. Conclusions In our study, a novel signature was constructed with paired DEirlncRNAs (regardless of their expression), which holds significant clinical predictive value and is a potential breakthrough for personalized management of GBM.
... Some researchers have developed prognostic models using lncRNAs. For example, Zhou et al. [61] developed an immune-related prognostic model using lncRNAs that can divide patients into highrisk and low-risk groups with a survival analysis log-rank test P < 0.05. Additionally, some researchers have incorporated imaging features to create prognostic models. ...
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Background Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults. This study aimed to construct immune-related long non-coding RNAs (lncRNAs) signature and radiomics signature to probe the prognosis and immune infiltration of GBM patients. Methods We downloaded GBM RNA-seq data and clinical information from The Cancer Genome Atlas (TCGA) project database, and MRI data were obtained from The Cancer Imaging Archive (TCIA). Then, we conducted a cox regression analysis to establish the immune-related lncRNAs signature and radiomics signature. Afterward, we employed a gene set enrichment analysis (GSEA) to explore the biological processes and pathways. Besides, we used CIBERSORT to estimate the abundance of tumor-infiltrating immune cells (TIICs). Furthermore, we investigated the relationship between the immune-related lncRNAs signature, radiomics signature and immune checkpoint genes. Finally, we constructed a multifactors prognostic model and compared it with the clinical prognostic model. Results We identified four immune-related lncRNAs and two radiomics features, which show the ability to stratify patients into high-risk and low-risk groups with significantly different survival rates. The risk score curves and Kaplan–Meier curves confirmed that the immune-related lncRNAs signature and radiomics signature were a novel independent prognostic factor in GBM patients. The GSEA suggested that the immune-related lncRNAs signature were involved in L1 cell adhesion molecular (L1CAM) interactions and the radiomics signature were involved signaling by Robo receptors. Besides, the two signatures was associated with the infiltration of immune cells. Furthermore, they were linked with the expression of critical immune genes and could predict immunotherapy’s clinical response. Finally, the area under the curve (AUC) (0.890,0.887) and C-index (0.737,0.817) of the multifactors prognostic model were greater than those of the clinical prognostic model in both the training and validation sets, indicated significantly improved discrimination. Conclusions We identified the immune-related lncRNAs signature and tradiomics signature that can predict the outcomes, immune cell infiltration, and immunotherapy response in patients with GBM.
... New GBM molecular markers are required from recently recognized biological avenues, such as tissue-specific long non-coding RNAs and their epigenetic influence [17]. Advanced statistical methodology are warranted to assist in prognostic accuracy [19]. The current issue is that an imperfect understanding of GBM potentially accounts for such failures and has hastened the need to identify nuances in associated biocompatible nano-molecules to combat the challenge in visualization and grading GBM tumors towards durable effective therapeutic responses [20,21]. ...
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The heterogeneity of the glioma subtype glioblastoma multiforme (GBM) challenges effective neuropathological treatment. The reliance on in vitro studies and xenografted animal models to simulate human GBM has proven ineffective. Currently, a dearth of knowledge exists regarding the applicability of cell line biomolecules to the realm of GBM pathogenesis. Our study’s objectives were to address this preclinical issue and assess prominin-1, ICAM-1, PARTICLE and GAS5 as potential GBM diagnostic targets. The methodologies included haemoxylin and eosin staining, immunofluorescence, in situ hybridization and quantitative PCR. The findings identified that morphology correlates with malignancy in GBM patient pathology. Immunofluorescence confocal microscopy revealed prominin-1 in pseudo-palisades adjacent to necrotic foci in both animal and human GBM. Evidence is presented for an ICAM-1 association with degenerating vasculature. Significantly elevated nuclear PARTICLE expression from in situ hybridization and quantitative PCR reflected its role as a tumor activator. GAS5 identified within necrotic GBM validated this potential prognostic biomolecule with extended survival. Here we present evidence for the stem cell marker prominin-1 and the chemotherapeutic target ICAM-1 in a glioma animal model and GBM pathology sections from patients that elicited alternative responses to adjuvant chemotherapy. This foremost study introduces the long non-coding RNA PARTICLE into the context of human GBM pathogenesis while substantiating the role of GAS5 as a tumor suppressor. The validation of GBM biomarkers from cellular models contributes to the advancement towards superior detection, therapeutic responders and the ultimate attainment of promising prognoses for this currently incurable brain cancer.
... LncRNAs can affect cell invasion, migration, proliferation, apoptosis, and chemoresistance through their interactions with various cancer-related signaling pathways [33][34][35][36][37][38][39][40][41][42][43]. Because lncRNAs exhibit tissue-specific, cell-type-specific, disease-specific, and developmental stage-specific expression patterns and have a relatively stable structure, detecting one or more lncRNAs in body fluids or tumor tissues can serve as an effective biomarker for early screening, diagnosis, prognosis, and risk prediction in glioblastoma [38,[44][45][46][47]. ...
... For example, the lncRNA Mirt2 is a negative feedback regulator of excessive inflammatory responses [13], and the lncRNA Carlr can interact with the activated NF-κB transcription factor complex [14]. Moreover, lncRNAs can play biological roles in transcriptional regulation, epigenetic modification, and posttranscriptional regulation and regulate the occurrence and development of diverse animal and human diseases, including mastitis in dairy cows [15][16][17]. However, the effects of lncRNA expression profiles and mRNA-lncRNA regulatory networks in mastitis remain largely unexplored. ...
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Background The infection of bovine mammary glands by pathogenic microorganisms not only causes animal distress but also greatly limits the development of the dairy industry and animal husbandry. A deeper understanding of the host’s initial response to infection may increase the accuracy of selecting drug-resistant animals or facilitate the development of new preventive or therapeutic intervention strategies. In addition to their functions of milk synthesis and secretion, bovine mammary epithelial cells (BMECs) play an irreplaceable role in the innate immune response. To better understand this process, the current study identified differentially expressed long noncoding lncRNAs (DE lncRNAs) and mRNAs (DE mRNAs) in BMECs exposed to Escherichia coli lipopolysaccharide (LPS) and further explored the functions and interactions of these lncRNAs and mRNAs. Results In this study, transcriptome analysis was performed by RNA sequencing (RNA-seq), and the functions of the DE mRNAs and DE lncRNAs were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Next, we constructed a modulation network to gain a deeper understanding of the interactions and roles of these lncRNAs and mRNAs in the context of LPS-induced inflammation. A total of 231 DE lncRNAs and 892 DE mRNAs were identified. Functional enrichment analysis revealed that pathways related to inflammation and the immune response were markedly enriched in the DE genes. In addition, research results have shown that cell death mechanisms, such as necroptosis and pyroptosis, may play key roles in LPS-induced inflammation. Conclusions In summary, the current study identified DE lncRNAs and mRNAs and predicted the signaling pathways and biological processes involved in the inflammatory response of BMECs that might become candidate therapeutic and prognostic targets for mastitis. This study also revealed several possible pathogenic mechanisms of mastitis.
... For example, 18 autophagy-related lncRNAs were identified to construct a prognostic signature in breast cancer [13]. Other immune-related 6 lncRNAs were used to establish a prognostic signature in glioma [14]. ...
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Background Pancreatic adenocarcinoma is one of the most lethal tumors in the world with a poor prognosis. Thus, an accurate prediction model, which identify patients within high risk of pancreatic adenocarcinoma is needed to adjust the treatment and elevate the prognosis of these patients. Methods We obtained RNAseq data of The Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma (PAAD) from UCSC Xena database, identified immune-related lncRNAs (irlncRNAs) by correlation analysis, and identified differential expressed irlncRNAs (DEirlncRNAs) between pancreatic adenocarcinoma tissues from TCGA and normal pancreatic tissues from TCGA and Genotype-Tissue Expression (GTEx). Further univariate and lasso regression analysis were performed to construct prognostic signature model. Then, we calculated the areas under curve and identified the best cut-off value to identify high- and low-risk patients with pancreatic adenocarcinoma. The clinical characteristics, immune cell infiltration, immunosuppressive microenvironment, and chemoresistance were compared between high- and low-risk patients with pancreatic adenocarcinoma. Results We identified 20 DEirlncRNA pairs and grouped the patients by the best cut-off value. We proved that our prognostic signature model possesses a remarkable efficiency to predict prognosis of PAAD patients. The AUC for ROC curve was 0.905 for 1-year prediction, 0.942 for 2-year prediction, and 0.966 for 3-year prediction. Patients in high-risk group have poor survival rate and worse clinical characteristics. We also proved that patients in high-risk groups were in immunosuppressive status and may be resistant to immunotherapy. Anti-cancer drug evaluation was performed based on in-silico predated tool, such as paclitaxel, sorafenib, and erlotinib, may be suitable for PAAD patients in high-risk group. Conclusions Overall, our study constructed a novel prognostic risk model based on pairing irlncRNAs, exhibited a promising prediction value in patients with pancreatic adenocarcinoma. Our prognostic risk model may help distinguish PAAD patients suitable for medical treatments.
... A large number of lncRNAs have been identified to be aberrantly expressed and could serve as promising biomarkers in glioma (26)(27)(28). For instance, an analysis on lncRNA profiling in GBM and normal brains suggested that a survival model consisted of 9 lncRNAs could accurately predict the OS of patients with GBM (29). ...
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The antisense transcript of SATB2 protein (SATB2-AS1) is a novel long non-coding RNA (lncRNA) which is involved in the development of colorectal cancer, breast cancer and hepatocellular carcinoma. In the present study, it was aimed to investigate the consequent situation of SATB2-AS1 in tissue and cell lines of glioma. The expression of SATB2-AS1 in glioma cases was analyzed in The Cancer Genome Atlas datasets. The glycolytic metabolism was determined in glioma cells by detection of extracellular glucose level, oxygen consumption rate and extracellular acidification rate. Cell Counting Kit-8 assay and flow cytometry were used to assess cell proliferation and apoptosis in glioma cells. The interaction between SATB2-AS1 and microRNA (miR)-671-5p was verified by bioinformatic analysis, reverse transcription-quantitative PCR, dual luciferase reporter assay and RNA immunoprecipitation assay. The expression levels of the downstream targets of SATB2-AS1 were studied by western blotting. Results demonstrated that SATB2-AS1 was a downregulated lncRNA in low grade glioma and glioblastoma. Gain-of-function assay demonstrated that SATB2-AS1 inhibited cell proliferation, and glycolytic metabolism, while induced cell apoptosis in glioma cells. SATB2-AS1 sponged and suppressed the expression of an oncogenic miRNA miR-671-5p. By regulation of miR-671-5p, SATB2-AS1 upregulated cerebellar degeneration related protein 1 (CDR1) and Visinin-like 1 (VSNL1) expression in glioma cells. miR-671-5p overexpression partially reversed the antitumor effect of SATB2-AS1 in glioma. In conclusion, the current study demonstrated that there was a downregulation of SATB2-AS1 in glioma, and SATB2-AS1 regulated miR-671-5p/CDR1 axis and miR-671-5p/VSNL1 axis in glioma.
... start codons, promoter conserved regions, stop codons or open reading frames (Ulitsky et al., 2011;Guttman and Rinn, 2012). However, in recent years, an increasing number of lncRNAs with biological functions have been identified, and lncRNAs play important roles in many biological activities, such as participating in cell proliferation (Liu et al., 2018;Qin et al., 2018), differentiation (Song et al., 2016;Touat Todeschini et al., 2017) and apoptosis Nan et al., 2017) and promoting myogenic cell differentiation and injury-induced muscle regeneration (Wang et al., 2015), fat deposition (Wang et al., 2017), lactation (Yu et al., 2017), reproduction (Wang et al., 2014) and immunity (Zhou et al., 2017). lncRNAs have also become a hot spot for research in different scientific directions. ...
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Long noncoding RNAs (lncRNAs) were important regulators affecting the cellular reprogramming process. Previous studies from our group have demonstrated that small molecule compounds can induce goat ear fibroblasts to reprogram into mammary epithelial cells with lactation function. In this study, we used lncRNA-Sequencing (lncRNA-seq) to analyze the lncRNA expression profile of cells before and after reprogramming (CK vs. 5i8 d). The results showed that a total of 3,970 candidate differential lncRNAs were detected, 1,170 annotated and 2,800 new lncRNAs. Compared to 0 d cells, 738 lncRNAs were significantly upregulated and 550 were significantly downregulated in 8 d cells. Heat maps of lncrnas and target genes with significant differences showed that the fate of cell lineages changed. Functional enrichment analysis revealed that these differently expressed (DE) lncRNAs target genes were mainly involved in signaling pathways related to reprogramming and mammary gland development, such as the Wnt signaling pathway, PI3K-Akt signaling pathway, arginine and proline metabolism, ECM-receptor interaction, and MAPK signaling pathway. The accuracy of sequencing was verified by real-time fluorescence quantification (RT-qPCR) of lncRNAs and key candidate genes, and it was also demonstrated that the phenotype and genes of the cells were changed. Therefore, this study offers a foundation for explaining the molecular mechanisms of lncRNAs in chemically induced mammary epithelial cells.
... Long noncoding RNAs (lncRNAs) are a class of noncoding RNAs with transcript lengths ≥ 200 nt, and they play a crucial role in regulating gene expression. Studies have shown that lncRNAs have many biological functions, such as participating in cell proliferation [8,9], differentiation [10,11], apoptosis [12,13], promoting myoblast differentiation and injury-induced muscle regeneration [14], fat deposition [15], lactation [16], reproduction [17], immunity [18] and many other life processes. Studies on humans and model animals have shown that lncRNA is involved in mammalian mammary gland development and regulation of lactation processes [16,19]. ...