scholarly journals SYDE1 Acts as an Oncogene in Glioma and has Diagnostic and Prognostic Values

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhenyuan Han ◽  
Xiaodong Zhuang ◽  
Biao Yang ◽  
Lihui Jin ◽  
Pengjie Hong ◽  
...  

Objectives: Gliomas remain one of serious public health problems worldwide which demand further and deeper investigation. The aim of this study was to explore the association between synapse defective protein 1 homolog 1 (SYDE1) and gliomas via public database analysis and in vitro validation to determine the potential diagnostic and prognostic values.Methods and Results: Compared with healthy brain tissues, there was a significant increase in SYDE1 expression in glioma tissues. Additionally, SYDE1 exhibited higher expression levels in glioma patients with unfavorable clinicopathological factors. In vitro knockdown of SYDE1 in glioma cell lines A172 inhibited their migrative and invasive ability but not the proliferative ability. GO and KEGG pathway analysis of the top 100 genes coexpressed with SYDE1 showed enrichments of tumor-associated terms. Further bioinformatic analysis revealed that the SNHG16/hsa-miR-520e/SYDE1 axis might be involved in glioma development.Conclusions:SYDE1 is expressed at higher levels in gliomas than in healthy brains, and can promote metastasis and invasion but not proliferation of gliomas. Furthermore, SYDE1 has values in the diagnosis and prognosis prediction of gliomas.

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Jiacheng Wu ◽  
Shui Liu ◽  
Yien Xiang ◽  
Xianzhi Qu ◽  
Yingjun Xie ◽  
...  

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and is associated with a high mortality rate and poor treatment efficacy. In an attempt to investigate the mechanisms involved in the pathogenesis of HCC, bioinformatic analysis and validation by qRT-PCR were performed. Three circRNA GEO datasets and one miRNA GEO dataset were selected for this purpose. Upon combined biological prediction, a total of 11 differentially expressed circRNAs, 15 differentially expressed miRNAs, and 560 target genes were screened to construct a circRNA-related ceRNA network. GO analysis and KEGG pathway analysis were performed for the 560 target genes. To further screen key genes, a protein-protein interaction network of the target genes was constructed using STRING, and the genes and modules with higher degree were identified by MCODE and CytoHubba plugins of Cytoscape. Subsequently, a module was screened out and subjected to GO enrichment analysis and KEGG pathway analysis. This module included eight genes, which were further screened using TCGA. Finally, UBE2L3 was selected as a key gene and the hsa_circ_0009910–miR-1261–UBE2L3 regulatory axis was established. The relative expression of the regulatory axis members was confirmed by qRT-PCR in 30 pairs of samples, including HCC tissues and adjacent nontumor tissues. The results suggested that hsa_circ_0009910, which was upregulated in HCC tissues, participates in the pathogenesis of HCC by acting as a sponge of miR-1261 to regulate the expression of UBE2L3. Overall, this study provides support for the possible mechanisms of progression in HCC.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8409 ◽  
Author(s):  
Shi-shuo Wang ◽  
Zhi-guang Huang ◽  
Hua-yu Wu ◽  
Rong-quan He ◽  
Li-hua Yang ◽  
...  

Background Hepatocellular carcinoma (HCC) is the second-highest cause of malignancy-related death worldwide, and many physiological and pathological processes, including cancer, are regulated by microRNAs (miRNAs). miR-193a-3p is an anti-oncogene that plays an important part in health and disease biology by interacting with specific targets and signals. Methods In vitro assays were performed to explore the influences of miR-193a-3p on the propagation and apoptosis of HCC cells. The sequencing data for HCC were obtained from The Cancer Genome Atlas (TCGA), and the expression levels of miR-193a-3p in HCC and non-HCC tissues were calculated. The differential expression of miR-193a-3p in HCC was presented as standardized mean difference (SMD) with 95% confidence intervals (CIs) in Stata SE. The impact of miR-193a-3p on the prognoses of HCC patients was determined by survival analysis. The potential targets of miR-193a-3p were then predicted using miRWalk 2.0 and subjected to enrichment analyses, including Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Protein-Protein Interaction (PPI) network analysis. The interaction between miR-193a-3p and one predicted target, Cyclin D1 (CCND1), was verified by dual luciferase reporter assays and Pearson correlation analysis. Results MiR-193a-3p inhibited the propagation and facilitated the apoptosis of HCC cells in vitro. The pooled SMD indicated that miR-193a-3p had a low level of expression in HCC (SMD: −0.88, 95% CI [−2.36 −0.59]). Also, HCC patients with a higher level of miR-193a-3p expression tended to have a favorable overall survival (OS: HR = 0.7, 95% CI [0.43–1.13], P = 0.14). For the KEGG pathway analysis, the most related pathway was “proteoglycans in cancer”, while the most enriched GO term was “protein binding”. The dual luciferase reporter assays demonstrated the direct interaction between miR-193a-3p and CCND1, and the Pearson correlation analysis suggested that miR-193a-3p was negatively correlated with CCND1 in HCC tissues (R =  − 0.154, P = 0.002). Conclusion miR-193a-3p could suppress proliferation and promote apoptosis by targeting CCND1 in HCC cells. Further, miR-193a-3p can be used as a promising biomarker for the diagnosis and treatment of HCC in the future.


2018 ◽  
Vol 45 (5) ◽  
pp. 1986-1998 ◽  
Author(s):  
Xiaomei Liu ◽  
Qing Zhang ◽  
Weixiao Wang ◽  
Dongjiao Zuo ◽  
Jing Wang ◽  
...  

Background/Aims: Multiple sclerosis (MS) is an autoimmune disease in the central nervous system associated with demyelination and axonal injury. Astrocyte activation is involved in the pathogenesis of MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. This study was designed to find potential lncRNAs in EAE mice and activated astrocytes. Methods: we performed microarray analysis of lncRNAs from the brain tissues of EAE mice and primary mouse astrocytes treated with IL-9(50 ng/ml). 12 lncRNAs were validated through real-time PCR. Gene ontology and KEGG pathway analysis were applied to explore the potential functions of lncRNAs. Results: Differentially expressed 3300 lncRNAs and 3250 mRNAs were in the brain tissues of EAE mice, and 3748 lncRNAs and 3332 mRNAs were in activated astrocytes. Notably, there were 2 co-up-regulated lncRNAs and 3 co-down-regulated lncRNAs both in the brain tissues of EAE mice and in activated astrocytes, including Gm14005, Gm12478, mouselincRNA1117, AK080435, and mouselincRNA0681, which regulate the ER calcium flux kinetics, zinc finger protein and cell apoptosis. Similarly, there were 7 mRNAs co-up-regulated and 2 mRNAs co-down-regulated both in vivo and in vitro. Gene ontology and KEGG pathway analysis showed that the biological functions of differentially expressed mRNAs were associated with metabolism, development and inflammation. The results of realtime PCR validation were consistent with the data from the microarrays. Conclusions: Our data uncovered the expression profiles of lncRNAs and mRNAs in vivo and in vitro, which may help delineate the mechanisms of astrocyte activation during MS/EAE process.


2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Guo-zhong Yi ◽  
Wei Xiang ◽  
Wen-yan Feng ◽  
Zi-yang Chen ◽  
Yao-min Li ◽  
...  

TMZ resistance remains one of the main reasons why treatment of glioblastoma (GBM) fails. In order to investigate the underlying proteins and pathways associated with TMZ resistance, we conducted a cytoplasmic proteome research of U87 cells treated with TMZ for 1 week, followed by differentially expressed proteins (DEPs) screening, KEGG pathway analysis, protein–protein interaction (PPI) network construction, and validation of key candidate proteins in TCGA dataset. A total of 161 DEPs including 65 upregulated proteins and 96 downregulated proteins were identified. Upregulated DEPs were mainly related to regulation in actin cytoskeleton, focal adhesion, and phagosome and PI3K-AKT signaling pathways which were consistent with our previous studies. Further, the most significant module consisted of 28 downregulated proteins that were filtered from the PPI network, and 9 proteins (DHX9, HNRNPR, RPL3, HNRNPA3, SF1, DDX5, EIF5B, BTF3, and RPL8) among them were identified as the key candidate proteins, which were significantly associated with prognosis of GBM patients and mainly involved in ribosome and spliceosome pathway. Taking the above into consideration, we firstly identified candidate proteins and pathways associated with TMZ resistance in GBM using proteomics and bioinformatic analysis, and these proteins could be potential biomarkers for prevention or prediction of TMZ resistance in the future.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8216 ◽  
Author(s):  
Yue Li ◽  
Xintao Zhu ◽  
Ming Zhang ◽  
Huasheng Tong ◽  
Lei Su

Background Liver injury is a common and important clinical issue of severe heat stress (HS), which has toxic effects and promotes subsequent multiple organ failure. The pathogenesis of HS-induced liver injury has not been fully elucidated. Passively injured hepatocytes also drive liver injury. Exosomes, extracellular vesicles secreted by hepatocytes as “danger signals,” mediate the intercellular transportation of diverse functional protein cargoes and modulate the biological processes of target cells. However, whether hepatocyte exosomes are involved in HS-induced liver injury has not been reported. The purpose of the current study was to clarify the release of hepatocyte exosomes under HS conditions and to explore their role in mediating HS-induced liver injury. Methods HS was induced in hepatocytes or mice by hyperthermic treatment at 43.0 °C for 1 h. Exosomes from control and HS-exposed hepatocytes were isolated by standard differential ultracentrifugation. The hepatocyte exosomes were characterized, and the differentially expressed proteins of the control and HS exosomes were identified by isobaric tags for relative and absolute quantitation (iTRAQ) mass spectrometry and subjected to Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. Recipient hepatocytes were treated with control or HS exosomes, whereas in vivo, the exosomes were infused into mice. The internalization of HS hepatocyte exosomes by hepatocytes or the liver was tracked. The effect of HS exosomes on the activation of the NOD-like receptor signaling pathway and liver injury was demonstrated in vitro and in vivo. Results HS induced an increase in the release of exosomes from hepatocytes, which were internalized by recipient liver cells in vitro and taken up by the liver in vivo. HS significantly changed the proteomic profiles of hepatocyte exosomes based on the iTRAQ analysis. The KEGG pathway analysis revealed the enrichment of proteins associated with injury and inflammatory signaling pathways, especially the NOD-like receptor signaling pathway, the activity of which was upregulated. Subsequently, the capacity of HS hepatocyte exosomes to activate the NOD-like receptor signaling pathway was verified and found to aggrevate liver damage and inflammation in vitro and in vivo. Conclusions This study is the first preliminary study to demonstrate the induction of acute liver injury by hepatic exosomes in the setting of severe HS and reveals potentially related pathways. These results provide a basis for future research and the identification of new targets for clinical intervention.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Cong Xu ◽  
Ting Liang ◽  
Fangrong Zhang ◽  
Jing Liu ◽  
Yunfeng Fu

Abstract Background tRNA-derived fragments have been reported to be key regulatory factors in human tumors. However, their roles in the progression of multiple myeloma remain unknown. Results This study employed RNA-sequencing to explore the expression profiles of tRFs/tiRNAs in new diagnosed MM and relapsed/refractory MM samples. The expression of selected tRFs/tiRNAs were further validated in clinical specimens and myeloma cell lines by qPCR. Bioinformatic analysis was performed to predict their roles in multiple myeloma progression.We identified 10 upregulated tRFs/tiRNAs and 16 downregulated tRFs/tiRNAs. GO enrichment and KEGG pathway analysis were performed to analyse the functions of 1 significantly up-regulated and 1 significantly down-regulated tRNA-derived fragments. tRFs/tiRNAs may be involved in MM progression and drug-resistance. Conclusion tRFs/tiRNAs were dysregulated and could be potential biomarkers for relapsed/refractory MM.


PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5721 ◽  
Author(s):  
Diangeng Li ◽  
Pengtao Bao ◽  
Zhiwei Yin ◽  
Lei Sun ◽  
Jin Feng ◽  
...  

Background HIV-associated encephalitis (HIVE) is one of the common complications of HIV infection, and the pathogenesis of HIVE remains unclear, while lncRNA might be involved it. In this study, we made re-annotation on the expression profiling from the HIVE study in the public database, identified the lncRNA that might be involved in HIVE, and explored the possible mechanism. Methods In the GEO public database, the microarray expression profile (GSE35864) of three regions of brain tissues (white matter, frontal cortex and basal ganglia brain tissues) was chosen, updated annotation was performed to construct the non-cording-RNA (ncRNA) microarray data. Morpheus was used to identify the differential expressed ncRNA, and Genbank of NCBI was used to identify lncRNAs. The StarBase, PITA and miRDB databases were used to predict the target miRNAs of lncRNA. The TargetScan, PicTar and MiRanda databases were used to predict the target genes of miRNAs. The GO and KEGG pathway analysis were used to make function analysis on the targets genes. Results Seventeen differentially expressed lncRNAs were observed in the white matter of brain tissues, for which 352 target miRNAs and 6,659 target genes were predicted. The GO function analysis indicated that the lncRNAs were mainly involved in the nuclear transcription and translation processes. The KEGG pathway analysis showed that the target genes were significantly enriched in 33 signal pathways, of which 11 were clearly related to the nervous system function. Discussion The brand-new and different microarray results can be obtained through the updated annotation of the chips, and it is feasible to identify lncRNAs from ordinary chips. The results suggest that lncRNA may be involved in the occurrence and development of HIVE, which provides a new direction for further research on the diagnosis and treatment of HIVE.


Biomaterials ◽  
2010 ◽  
Vol 31 (24) ◽  
pp. 6201-6206 ◽  
Author(s):  
Ping Wang ◽  
Lei Li ◽  
Cheng Zhang ◽  
Qunfang Lei ◽  
Wenjun Fang

Author(s):  
Peirong Li ◽  
Xinru Li ◽  
Wei Wang ◽  
Xiaoling Tan ◽  
Xiaoqi Wang ◽  
...  

Abstract The oriental armyworm, Mythimna separata (Walker) is a serious pest of agriculture that does particular damage to Gramineae crops in Asia, Europe, and Oceania. Metamorphosis is a key developmental stage in insects, although the genes underlying the metamorphic transition in M. separata remain largely unknown. Here, we sequenced the transcriptomes of five stages; mature larvae (ML), wandering (W), and pupation (1, 5, and 10 days after pupation, designated P1, P5, and P10) to identify transition-associated genes. Four libraries were generated, with 22,884, 23,534, 26,643, and 33,238 differentially expressed genes (DEGs) for the ML-vs-W, W-vs-P1, P1-vs-P5, and P5-vs-P10, respectively. Gene ontology enrichment analysis of DEGs showed that genes regulating the biosynthesis of the membrane and integral components of the membrane, which includes the cuticular protein (CP), 20-hydroxyecdysone (20E), and juvenile hormone (JH) biosynthesis, were enriched. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that DEGs were enriched in the metabolic pathways. Of these DEGs, thirty CP, seventeen 20E, and seven JH genes were differentially expressed across the developmental stages. For transcriptome validation, ten CP, 20E, and JH-related genes were selected and verified by real-time PCR quantitative. Collectively, our results provided a basis for further studies of the molecular mechanism of metamorphosis in M. separata.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kirsten P. Stone ◽  
Sujoy Ghosh ◽  
Jean Paul Kovalik ◽  
Manda Orgeron ◽  
Desiree Wanders ◽  
...  

AbstractThe initial sensing of dietary methionine restriction (MR) occurs in the liver where it activates an integrated stress response (ISR) that quickly reduces methionine utilization. The ISR program is regulated in part by ATF4, but ATF4’s prototypical upstream regulator, eIF2α, is not acutely activated by MR. Bioinformatic analysis of RNAseq and metabolomics data from liver samples harvested 3 h and 6 h after initiating MR shows that general translation is inhibited at the level of ternary complex formation by an acute 50% reduction of hepatic methionine that limits formation of initiator methionine tRNA. The resulting ISR is induced by selective expression of ATF4 target genes that mediate adaptation to reduced methionine intake and return hepatic methionine to control levels within 4 days of starting the diet. Complementary in vitro experiments in HepG2 cells after knockdown of ATF4, or inhibition of mTOR or Erk1/2 support the conclusion that the early induction of genes by MR is partially dependent on ATF4 and regulated by both mTOR and Erk1/2. Taken together, these data show that initiation of dietary MR induces an mTOR- and Erk1/2-dependent stress response that is linked to ATF4 by the sharp, initial drop in hepatic methionine and resulting repression of translation pre-initiation.


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