Mechanical characteristics of BMSCs-intervened sciatic nerve in chronic alcohol-intoxicated animal model.

OBJECTIVE: To study the mechanical properties of sciatic nerve in rats with chronic alcoholism (CA) and intervened with bone marrow mesenchymal stem cells (BMSCs) and to provide biomechanical basis for clinical practice. METHODS: the serum of the BMSCs-intervened CA rats was sampled and determined the contents of malondialdehyde (MDA), metallothionein (CAS, MT), and Glutathione/r -glutamyl cysteinyl/glycine (GSH); meanwhile, the rats' sciatic nerve was tested the tensile and observed the histomorphological changes. RESULTS: The mechanical properties of sciatic nerve in BMSCs-intervened CA rats, as well as the serum levels of MT and GSH, were significantly different from those in the basic fibroblast growth factor (bFGF)-intervened CA rats (p < 0.05). CONCLUSIONS: BMSCs intervention can restore the levels of MT, GSH, MDA, histomorphology, and tensile mechanical properties in CA animal model, and its effects on repairing sciatic nerve are obvious.

Identification of human lactate dehydrogenase A inhibitors with anti-osteosarcoma activity through cell-based phenotypic screening.

Human lactate dehydrogenase A plays a key role in the glycolytic process, the inhibition of the enzyme is therefore considered of interest in developing anticancer therapeutics. However, due to the highly polar nature of hLDHA binding pocket, it is very challenge to discover potent cellular active hLDHA inhibitor. Combined a cell-based phenotypic screening assay with a primary enzymatic assay, we discovered three cellular active hLDHA inhibitors, namely 38, 63, and 374, which reduced MG-63 cell proliferation with IC50 values of 6.47, 2.93, and 6.10 µM, respectively, and inhibited hLDHA with EC50 values of 3.03, 0.63, and 3.26 µM, respectively.

miR-487b and TRAK2 that form an axis to regulate the aggressiveness of osteosarcoma, are potential therapeutic targets and prognostic biomarkers.

To investigate the effect of microRNA-487b (miR-487b) as well as the underlying mechanism in osteosarcoma (OS). Data downloaded from the Gene Expression Omnibus (GEO) database were used to analyze the expression and prognostic value of miR-487b/TRAK2. Cell counting kit-8, colony formation, and transwell assays were performed to investigate the biological functions of miR-487b and TRAK2. Luciferase reporter assay was applied to confirm the interactions between miR-487b and TRAK2. miR-487b was overexpressed in OS tissues and was inversely associated with the prognosis of OS patients. We discovered that miR-487b could contribute to the proliferative, clonogenic, invasive, and migratory capabilities of OS cells. Through target prediction using miRWalk and differential expression analysis based on the GEO data set, trafficking kinesin protein 2 (TRAK2) was recognized as a potential target of miR-487b, which was further verified by luciferase reporter assay. The expression of TRAK2 was decreased in OS tissues compared with normal tissues and was positively correlated with the prognosis of OS patients. A negative relevance was presented between the expression of miR-487b and TRAK2 in OS cells. Of note, further mechanistic analyses indicated that TRAK2 was implicated in the regulatory effect of miR-487b on the cell malignant behaviors in OS. To sum up, these results demonstrated that miR-487b played an oncogenic role in OS progression via directly targeting TRAK2, which could advance the development of cancer treatment.

LncRNA AWPPH promotes osteosarcoma progression via activation of Wnt/ß-catenin pathway through modulating miR-93-3p/FZD7 axis.

Long noncoding RNAs (lncRNAs) have important regulatory roles in osteosarcoma (OS) progression. Recent researches have shown lncRNA AWPPH promotes lung cancer progression and bladder cancer development. Yet, the function of AWPPH in OS is unknown. In this research, results indicated AWPPH levels were increased in OS tissues in contrast to paracancerous controls. Up-regulated AWPPH was associated with advanced stage, tumor size and metastasis. Besides, AWPPH up-regulation indicated a low survival rate in OS patients. Silencing of AWPPH suppressed proliferation, migration and invasion of OS cells. Mechanistically, AWPPH was demonstrated to sponge miR-93-3p and promote FZD7 expression, causing activation of Wnt/ß-catenin. Inhibition of miR-93-3p effectively reversed the effects of AWPPH knockdown on OS cells. Collectively, our findings suggested AWPPH may be a prognostic biomarker and potential therapeutic target. AWPPH enhances FZD7-mediated activation of Wnt/ß-catenin by sponging miR-93-3p to promote OS progression.

Knockdown of lncRNA MEG3 inhibits viability, migration, and invasion and promotes apoptosis by sponging miR-127 in osteosarcoma cell.

Osteosarcoma (OS) is one of the most common bone malignancies and occurs almost exclusively in children and adolescents. This study aimed to explore the role of lncRNA maternally expressed gene 3 (MEG3) in OS cells growth and metastasis, and to uncover the possible underlying mechanism. In this study, the expressions of MEG3 in five OS cell lines (MG63, OS-732, SaOS, G292, and 143B) and in a human osteoblast cell line hFOB1.19 were measured by qRT-PCR analysis. The expressions of MEG3, miR-127, and ZEB1 in OS-732 cells were overexpressed or suppressed by transfection. Cell viability, migration, invasion, and apoptosis were then assessed. The results showed that MEG3 was highly expressed in OS cell lines when compared to hFOB1.19 cell. MEG3 silence significantly suppressed OS-732 cells growth and metastasis, as evidenced by the decreases in cell viability, migration, invasion, and increase in apoptotic cell rate. MEG3 acted as an endogenous sponge by binding to miR-127. More interestingly, MEG3 silence could not suppress OS-732 cells growth and metastasis when miR-127 was knocked down. ZEB1 was a target gene of miR-127, and miR-127 overexpression-induced impairments in cell growth and metastasis were attenuated when ZEB1 was overexpressed. Moreover,miR-127 suppression activated JNK and Wnt signaling pathways, while these activations were recovered by ZEB1 silence. To conclude, our findings suggest that lncRNA MEG3 promoted OS cells growth and metastasis in vitro through sponging miR-127. This study provides the evidence that MEG3 may be a potential therapeutic target for OS.

MicroRNA-136 promotes lipopolysaccharide-induced ATDC5 cell injury and inflammatory cytokine expression by targeting myeloid cell leukemia 1.

Osteoarthritis is the most frequent chronic bone and joint diseases in older populations all over the world. Lipopolysaccharide (LPS)-induced murine chondrogenic ATDC5 cell model has been widely used for testing new osteoarthritis therapeutic targets. This study aimed to explore the effects of microRNA-136 (miR-136) on LPS-induced ATDC5 cell injury and inflammatory cytokine expression, as well as underlying potential mechanism. We found that LPS remarkably inhibited ATDC5 cell viability, induced ATDC5 cell apoptosis, and upregulated the expression of inflammatory cytokines, including interleukin 1ß (IL-1ß), IL-6, IL-8, and tumor necrosis factor α (TNF-α; P < .01 or < .001). Moreover, LPS obviously upregulated the expression of miR-136 in ATDC5 cells (P < .05). Overexpression of miR-136 markedly exacerbated the LPS-induced ATDC5 cell viability inhibition, cell apoptosis enhancement, and inflammatory cytokine expression (P < .05), and suppression of miR-136 had opposite effects (P < .05). Myeloid cell leukemia 1 (Mcl-1) was a direct target gene of miR-136, which participated in the effect of miR-136 on LPS-induced ATDC5 cell inflammatory injury. Overexpression of Mcl-1 alleviated the LPS-induced inactivation of Wnt/ß-catenin and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathways, while suppression of Mcl-1 had opposite effects. To conclude, this study verified that miR-136 promoted LPS-induced ATDC5 cell injury and inflammatory cytokine expression by targeting Mcl-1, and Mcl-1 was involved in the regulatory effects of LPS on Wnt/ß-catenin and JAK/STAT signaling pathways in ATDC5 cells.

Knockdown of lncRNA HULC inhibits proliferation, migration, invasion, and promotes apoptosis by sponging miR-122 in osteosarcoma.

Osteosarcoma is a rare malignant bone tumor with high degree of malignancy. HULC (highly upregulated in liver cancer), a long noncoding RNA (lncRNA) was involved in hepatocellular carcinoma development and progression, but its underlying mechanism in osteosarcoma is unknown. The aim of this study was to explore the functional role of HULC in osteosarcoma. The study was conducted in human osteosarcoma cell lines and the expression of HULC in the cell lines was detected by qRT-PCR. Furthermore, the effects of HULC on tumorigenicity of osteosarcoma cells were evaluated by in vitro assays. Results revealed that HULC was highly expressed in osteosarcoma MG63 and OS-732 cells compared to osteoblast hFOB1.19 cells. Suppression of HULC in osteosarcoma cells inhibited cell viability, migration, invasion, and promoted apoptosis. HULC functioned as an endogenous sponge for miR-122, and its silence functioned through upregulating miR-122. HNF4G was a target of miR-122, and the effect of HNF4G on OS-732 cells was the same as HULC. Furthermore, overexpression of miR-122 inactivated PI3K/AKT, JAK/STAT, and Notch pathways by downregulation of HNF4G. These findings suggest that knockdown of HULC inhibited proliferation, migration, and invasion by sponging miR-122 in osteosarcoma cells. HULC may act as a novel therapeutic target for management of osteosarcoma.

LncRNA GAS5 Represses Osteosarcoma Cells Growth and Metastasis via Sponging MiR-203a.

BACKGROUND/AIMS: LncRNA GAS5, a growth suppressor, has been reported to exert anti-tumor actions in various cancers, whereas the exact mechanism underling the anti-tumor action is still unclear. This study was aimed to investigate the effect of lncRNA GAS5 on osteosarcoma and tried to decode the underling mechanisms. METHODS: Expressions of lncRNA GAS5 in MG-63 cells were silenced by shRNA transfection, while were overexpressed by vector transfection. Cell viability, migration, invasion and apoptosis were respectively assessed by MTT, Transwell assay and flow cytometry. Regulations between lncRNA GAS5 and miR-203a, as well as between miR-203a and TIMP2 were detected by qPCR, western blot and dual luciferase activity assay. RESULTS: LncRNA GAS5 was down-regulated in MG-63 and OS-732 cells compared to hFOB1.19 cells. Silence of lncRNA GAS5 significantly promoted MG-63 cells viability, migration and invasion, and up-regulated Cyclin D1, Cyclin B1, CDK1 and CDK4 expressions. miR-203a was negatively regulated by lncRNA GAS5. The promoting activities of lncRNA GAS5 silence on MG-63 cells growth and metastasis were reversed by miR-203a suppression. TIMP2 was a target of miR-203a and the anti-growth and anti-metastasis actions of miR-203a suppression were reversed by TIMP2 silence. Further, lncRNA GAS5 silence, miR-203a overexpression, and TIMP2 silence could activate PI3K/AKT/GSK3ß signaling while block NF-κB signaling. CONCLUSION: LncRNA GAS5 might be a tumor suppressor in osteosarcoma via sponging miR-203a, sequestering miR-203a away from TIMP2.

Long noncoding RNA LSINCT5 acts as an oncogene via increasing EZH2-induced inhibition of APC expression in osteosarcoma.

Long noncoding RNAs (lncRNAs) are recognized as a class of critical regulators in various tumors. Recently, lncRNA LSINCT5 has been reported to promote the progression of bladder cancer, ovarian cancer, gastric cancer, and breast cancer. However, the biological function of LSINCT5 remains elusive in osteosarcoma (OS). In our study, we found that LSINCT5 was significantly upregulated in OS tissues than in adjacent normal tissues. Additionally, the expression of LSINCT5 was inversely associated with the prognosis of patients with OS. LSINCT5 knockdown dramatically inhibited OS cell proliferation in vitro and tumor growth in vivo. Mechanistic exploration revealed that LSINCT5 interacted with EZH2 to suppress the expression of APC, a negative regulator of the Wnt/ß-catenin pathway. Moreover, rescue assays suggested that LSINCT5 exerted oncogenic roles by partially inhibiting APC expression in OS. In summary, our study demonstrated that LSINCT5 was a promising candidate for OS prognosis and therapy.

NAIF1 suppresses osteosarcoma progression and is regulated by miR-128.

Nuclear apoptosis-inducing factor 1 (NAIF1) acts as an oncogene and involves in tumorigenesis in several cancers. However, the expression and mechanism of NAIF1 in osteosarcoma remains unclear. In this study, we demonstrated the downregulation of NAIF1 expression in both osteosarcoma tissues and cell lines. We next explored the potential role of NAIF1 in osteosarcoma cell proliferation and migration. The result showed that overexpression of NAIF1 evidently suppressed the cell proliferation and invasion of osteosarcoma. Furthermore, we investigated the potential mechanisms accounting for dysregulation of NAIF1 in osteosarcoma. The bioinformatic prediction and luciferase reporter assay revealed that miR-128 is a direct upstream regulator of NAIF1 and regulates NAIF1 expression by binding the 3'-UTR of NAIF1. Consistent with previous study, we found that miR-128 was upregulated in both osteosarcoma tissues and cell lines. Moreover, miR-128 expression levels were inversely correlated with that of NAIF1 in osteosarcoma tissues. Finally, functional assay showed that miR-128 significantly suppressed osteosarcoma progression partially mediated by inhibiting NAIF1 expression. These data indicate that the miR-128 and its target gene NAIF1 played important roles by regulating OS cell proliferation and migration phenotype. SIGNIFICANCE OF THE STUDY: Osteosarcoma (OS) is the most common malignant bone tumour and the second leading cause of cancer-related death affecting children and adolescents. Nuclear apoptosis-inducing factor 1 (NAIF1) plays an inhibitory role in the initial steps of different carcinomas. However, the expression and mechanism of NAIF1 in osteosarcoma remains unclear. The data of this study indicated that the miR-128 and its target gene NAIF1 played important roles by regulating OS cell proliferation and migration phenotype. It was demonstrated that NAIF1 would demonstrate important regulative effects and may be a promising therapeutic target of OS.

Screening of Critical Genes and MicroRNAs in Blood Samples of Patients with Ruptured Intracranial Aneurysms by Bioinformatic Analysis of Gene Expression Data.

BACKGROUND This study aimed to identify more potential genes and miRNAs associated with the pathogenesis of intracranial aneurysms (IAs). MATERIAL AND METHODS The dataset of GSE36791 (accession number) was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened for in the blood samples from patients with ruptured IAs and controls, followed by functional and pathway enrichment analyses. In addition, gene co-expression network was constructed and significant modules were extracted from the network by WGCNA R package. Screening for miRNAs that could regulate DEGs in the modules was performed and an analysis of regulatory relationships was conducted. RESULTS A total of 304 DEGs (167 up-regulated and 137 down-regulated genes) were screened for in blood samples from patients with ruptured IAs compared with those from controls. Functional enrichment analysis showed that the up-regulated genes were mainly associated with immune response and the down-regulated DEGs were mainly concerned with the structure of ribosome and translation. Besides, six functional modules were significantly identified, including four modules enriched by up-regulated genes and two modules enriched by down-regulated genes. Thereinto, the blue, yellow, and turquoise modules of up-regulated genes were all linked with immune response. Additionally, 16 miRNAs were predicted to regulate DEGs in the three modules associated with immune response, such as hsa-miR-1304, hsa-miR-33b, hsa-miR-125b, and hsa-miR-125a-5p. CONCLUSIONS Several genes and miRNAs (such as miR-1304, miR-33b, IRS2 and KCNJ2) may take part in the pathogenesis of IAs.

Expression of the Circadian Clock Gene ARNTL associated with DNA repair gene and prognosis of patient with osteosarcoma.

PURPOSE: The study objects were to explore the correlation between the biological role of clock genes and clinical indicators in patients with osteosarcoma (OS). METHODS: We acquired the clinical information and RNA sequencing data of OS samples from the TARGET database. The protein-protein interaction (PPI) network and expression correlation analysis of clock genes were performed. Then, the functional enrichment analysis of clock genes was analyzed. The survival analysis of clock genes in patients of OS was carried out by univariate cox regression, Kaplan-Meier (KM) curve and multivariate cox regression methods. Moreover, the spearmen correlation analysis was performed to explore the correlation between clock genes and DNA repair genes in patients with OS. RESULTS: The PPI network and expression correlation analysis of clock genes indicated that the clock genes were highly correlated with each other. The survival analysis of clock genes found that clock gene ARNTL is a protective factor for the prognosis of patients with OS. We found that ARNTL was positively related to DNA repair genes and was involved in the biological process of DNA damage repair in patients with OS. CONCLUSIONS: ARNTL may affect the prognosis and chemotherapy response of patients with OS by regulating DNA repair pathways.

Erratum to "Identifying biomolecules and constructing a prognostic risk prediction model for recurrence in osteosarcoma" [J. Bone Oncol. 26 (2021) 100331].

[This corrects the article DOI: 10.1016/j.jbo.2020.100331.].

Identifying biomolecules and constructing a prognostic risk prediction model for recurrence in osteosarcoma.

INTRODUCTION: Osteosarcoma is a high-morbidity bone cancer with an unsatisfactory prognosis. The aim of this study is to develop novel potential prognostic biomarkers and construct a prognostic risk prediction model for recurrence in osteosarcoma. METHODS: By analyzing microarray data, univariate and multivariate Cox regression analyses were performed to screen prognostic RNA signatures and to build a prognostic model. The RNA signatures were validated using Kaplan-Meier curves. Then, we developed and validated a nomogram combining age, recurrence, metastatic, and Prognostic score (PS) models to predict the individual's overall survival at the 3- and 5-year points. Pathway enrichment of RNA was conducted based on the significant co-expressed RNAs. RESULTS: A total of 319 mRNAs and 14 lncRNAs were identified in the microarray data. One lncRNA (LINC00957) and six mRNAs (METL1, CA9, B3GALT4, ALDH1A1, LAMB3, and ITGB4) were identified as RNA signatures and showed good performances in survival prediction for both the training and validation cohorts. Cox regression analysis showed that the seven RNA signatures could independently predict overall survival. Furthermore, age, recurrence, metastatic, and PS models were identified as independent prognostic factors via univariate and multivariate Cox analyses (P < 0.05) and included in the prognostic nomogram. The C-index values for the 3- and 5-year overall survival predictions of the nomogram were 0.809 and 0.740, respectively. CONCLUSIONS: The current study provides the novel potential of seven RNA candidates as prognostic biomarkers. Nomograms were constructed to provide accurate and individualized survival prediction for recurrence in osteosarcoma patients.

CENPE, PRC1, TTK, and PLK4 May Play Crucial Roles in the Osteosarcoma Progression.

Osteosarcoma (OS) is a cancerous tumor in a bone. We aimed to identify the critical genes involved in OS progression, and then try to elucidate the molecular mechanisms of this disease. The microarray data of GSE32395 was used for the present study. We analyzed differentially expressed genes (DEGs) in OS cells compared with control group by Student's t-test. The significant enriched gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathways were analyzed for upregulated genes and downregulated genes, respectively. In addition, a protein-protein interaction (PPI) network was constructed. GO and KEGG enrichment analyses were conducted for genes in the PPI network. In total, 183 DEGs, including 100 upregulated DEGs and 83 downregulated DEGs were screened. The upregulated DEGs were significantly enriched in 2 KEGG pathways, such as "Glycosaminoglycan biosynthesis-chondroitin sulfate" and the downregulated DEGs were significantly enriched in 12 pathways, including "cell adhesion molecules," "pentose phosphate pathway" and "allograft rejection." GO enrichment analysis indicated that the upregulated DEGs were significantly involved in biological process, such as "multicellular organismal metabolic process" and "limb morphogenesis," while the downregulated DEGs were significantly enriched in biological process, such as "Positive regulation of pathway-restricted SMAD protein phosphorylation." The PPI network included 84 interactions and 51 nodes. The "glycosaminoglycan biosynthesis-chondroitin sulfate pathway," "microtubule motor activityfunction," and "regulation of mitosis process" were significantly enriched by genes in PPI network. In particular, CENPE, PRC1, TTK, and PLK4 had higher degrees in the PPI network. The interactions between TTK and PLK4 as well as CENPE and PRC1 may involve in the OS development. These 4 genes might be possible biomarkers for the treatment and diagnosis of OS.

Knockdown of hsa_circ_0059955 Induces Apoptosis and Cell Cycle Arrest in Nucleus Pulposus Cells via Inhibiting Itchy E3 Ubiquitin Protein Ligase.

BACKGROUND: Circular RNAs (circRNAs) play an important role in the progression of intervertebral disc (IVD) degeneration (IVDD). Using bioinformatics analysis, we have found that the expression of circRNA hsa_circ_0059955 was significantly downregulated in IVDD tissues. However, the relevant mechanism of hsa_circ_0059955 in the progression of IVDD remains unclear. METHODS: CCK-8 and flow cytometry assays were used to evaluate cell proliferation and apoptosis. In addition, Western blot assay was used to detect the expressions of ITCH, p73, CDK2 in nucleus pulposus (NP) cells. Moreover, a puncture-induced IVDD rat model was established to explore the role of hsa_circ_0059955 in IVDD. RESULTS: The level of hsa_circ_0059955 was significantly decreased in IVDD tissues from IVDD patients. Itchy E3 ubiquitin protein ligase (ITCH) is the host gene of hsa_circ_0059955, and downregulation of hsa_circ_0059955 significantly decreased the expression of ITCH in NP cells. In addition, downregulation of hsa_circ_0059955 markedly inhibited proliferation and induced apoptosis and cell cycle arrest in NP cells. Moreover, in vivo study illustrated that overexpression of hsa_circ_0059955 ameliorated IVDD in rats. CONCLUSION: Downregulation of hsa_circ_0059955 could induce apoptosis and cell cycle arrest in NP cells in vitro, while overexpression of hsa_circ_0059955 attenuated the IVDD in a puncture-induced rat model in vivo. Therefore, hsa_circ_0059955 might serve as a therapeutic target for the treatment of IVDD.

Mechanical properties of the sciatic nerve following combined transplantation of analytically extracted acellular allogeneic nerve and adipose-derived mesenchymal stem cells.

PURPOSE: To investigate the effects of Chemically Extracted Acellular Nerves (CEANs) when combined with Adipose-Derived mesenchymal Stem Cell (ADSC) transplantation on the repair of sciatic nerve defects in rabbits. METHODS: A total of 71 six-month-old Japanese rabbit were used in this study. Twenty rabbits served as sciatic nerve donors, while the other 51 rabbits were randomly divided into Autologous Nerve Transplantation Group (ANT, n=17), CEAN group (n=17) and CEAN-ADSCs group (n=17). In all these groups, the rabbit's left sciatic nerves were injured before the experiment, and the uninjured sciatic nerves on their right side were used as the control (CON). Electrophysiological tests were carried out and sciatic nerves were prepared for histomorphology and stretch testing at 24 weeks post-transplant. RESULTS: There were significant differences between ANT and Con groups in amplitude (AMP): P=0.031; motor nerve conduction velocity (MNCV): P=0.029; Maximum stress: P=0.029; and Maximum strain P=0.027. There were also differences between the CEAN and CEAN+ADSCs groups in AMP: P=0.026, MNCV: P=0.024; Maximum stress: P=0.025 and Maximum strain: P=0.030. No significant differences in these parameters were observed when comparing the ANT and CEAN+SACN groups (MNCV: P=0.071) or the CEAN and ANT groups (Maximum stress: P=0.069; Maximum strain P=0.077). CONCLUSION: Addition of ADSCs has a significant impact on the recovery of nerve function, morphology, and tensile mechanical properties following sciatic nerve injury.

Construction of Novel DNA Methylation-Based Prognostic Model to Predict Survival in Glioblastoma.

Glioblastoma (GBM) is a most aggressive primary cancer in brain with poor prognosis. This study aimed to identify novel tumor biomarkers with independent prognostic values in GBMs. The DNA methylation profiles were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus database. Differential methylated genes (DMGs) were screened from recurrent GBM samples using limma package in R software. Functional enrichment analysis was performed to identify major biological processes and signaling pathways. Furthermore, critical DMGs associated with the prognosis of GBM were screened according to univariate and multivariate cox regression analysis. A risk score-based prognostic model was constructed for these DMGs and prediction ability of this model was validated in training and validation data set. In total, 495 DMGs were identified between recurrent samples and disease-free samples, including 356 significantly hypermethylated and 139 hypomethylated genes. Functional and pathway items for these DMGs were mainly related to sensory organ development, neuroactive ligand-receptor interaction, pathways in cancer, etc. Five genes with abnormal methylation level were significantly correlated with prognosis according to survival analysis, such as ALX1, KANK1, NUDT12, SNED1, and SVOP. Finally, the risk model provided an effective ability for prognosis prediction both in training and validation data set. We constructed a novel prognostic model for survival prediction of GBMs. In addition, we identified five DMGs as critical prognostic biomarkers in GBM progression.

Prognostic Markers Identification in Glioma by Gene Expression Profile Analysis.

This study aimed to explore more gene markers associated with glioma or its prognosis. The glioma-related RNAseq data from the Gene Expression Omnibus database and The Cancer Genome Atlas dataset in UCSC Xena database were downloaded. There was a total of 971 tumor samples and 102 normal samples in the 2 datasets. The differentially expressed genes (DEGs) data between tumor and normal samples were analyzed, on which were then performed function and pathway enrichment analyses. Pearson correlation coefficient between DEGs was calculated to construct the coexpression network. Finally, prognostic genes were screened. A total of 634 upregulated and 769 downregulated DEGs were identified between tumor and control groups. These DEGs were significantly involved in 15 upregulated pathways, such as p53 signaling pathway, and 16 downregulated pathways, such as neuroactive ligand-receptor interaction, and cell adhesion molecules. In the coexpression network, pseudouridine synthase 7 (PUS7), EFR3 homolog B (EFR3B), and neuronal cell adhesion molecule (NRCAM) had the top three highest degrees. Additionally, 17 prognostic genes were selected, such as thrombospondin-1 (THBS1), caspase-8 (CASP8), glutamate ionotropic receptor AMPA type subunit 2 (GRIA2), GRIA4, and ADCYAP receptor type I (ADCYAP1R1). Pathways of p53 signaling pathway and neuroactive ligand-receptor interaction may play important roles in glioma progression. PUS7, EFR3B, and NRCAM may be potential biomarkers of glioma. THBS1, CASP8, GRIA2, GRIA4, and ADCYAP1R1 may serve as prognostic markers in glioma.

Sea cucumber Cucumaria frondosa fucoidan inhibits osteosarcoma adhesion and migration by regulating cytoskeleton remodeling.

Osteosarcoma (OS) has been demonstrated to be difficult to cure due to its potently malignant metastasis. Therefore, new therapeutic approaches blocking the metastatic potential of OS are urgently required to improve the outcomes for OS patients. In the present study, the anti­metastatic capacity of sea cucumber (Cucumaria frondosa) fucoidan (Cf­Fuc) was evaluated on osteosarcoma cells by cell adhesion assay, Transwell assay and U2OS cell migration assay. The underlying mechanism on the dynamic remodeling of the cytoskeleton was also explored. The present data indicated that Cf­Fuc could block the U2OS osteosarcoma cell adhesion to fibronectin and significantly inhibit U2OS cell migration. Cf­Fuc greatly impaired the migration capacity of U2OS cells, and the migrated distance and velocity of Cf­Fuc­treated cells were markedly reduced. Also, Cf­Fuc could impair the dynamic remodeling of the cytoskeleton possibly by suppressing the phosphorylation of focal adhesion kinase and paxillin, as well as the activation of the Rac1/PAK1/LIMK1/cofilin signaling axis. Collectively, the present findings provide a novel therapeutic potential of C. frondosa fucoidan for osteosarcoma metastasis.