Expression Profile of Peripheral Immune Cells-derived Coding and Long Non-coding RNAs in Patients With Proliferative Vitreoretinopathy
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Abstract Introduction: Peripheral immune response has been revealed to play a critical role in proliferative vitreoretinopathy (PVR). However, the reliable immune-related factors that are acting as prognostic indicators or therapeutic targets for PVR remain to explore further. Methods: In the current study, we applied whole-transcriptome sequencing to profile peripheral blood mononuclear cells (PBMCs) from PVR patients and also analyzed lncRNA-mRNA interactions in peripheral immune cells to explore the pathways that might mediate immunopathology and resultant retinal damage in PVR. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and Ingenuity Pathway Analysis (IPA) were employed to classify the function of these differentially expressed genes (DEGs). Results: Compared to the controls, there were 319 genes upregulated, and 191 genes downregulated in PVR patients. GO, and KEGG enrichment analyses as well as IPA showed that these upregulated genes were significantly enriched in immune-related and infection-relate terms. Immune-related gene NFKBIA , CXCL2 , and CXCL8 were detected as hub-genes in the co-expression network, while lncRNAs such as AC007032.1 , AC037198.2 , AL929472.2 , and SLED1 were highly co-expressed with them. lncRNA-mRNA interactions analysis also showed that putative targeted genes of these differentially expressed lncRNAs were also significantly enriched in immune-related or infection-relate pathways . Conclusion: Our study highlights the transformation of immune-related genes/pathways in PVR by comparing controls, and validates several critical genes and lncRNAs, which are serving as potential diagnostic markers for PVR patients.Keywords:
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This study explored the effects of the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on the development of uveal melanoma. Moreover, the role of the MALAT1/microRNA-608 (miR-608)/homeobox C4 (HOXC4) axis was assessed by evaluating the proliferation, invasion, and migration, as well as the cell cycle distribution of uveal melanoma in vitro after knocking down MALAT1 or HOXC4 and/or overexpression of miR-608 in uveal melanoma cells (MUM-2B and C918). Moreover, the effects of the MALAT1/miR-608/HOXC4 axis in uveal melanoma in vivo were further evaluated by injecting the C918 cells into the NOD/SCID mice. HOXC4 was found to be a gene upregulated in uveal melanoma, while knockdown of its expression resulted in suppression of uveal melanoma cell migration, proliferation, and invasion, as well as cell cycle progression. In addition, the upregulation of miR-608 reduced the expression of HOXC4 in the uveal melanoma cells, which was rescued by overexpression of MALAT1. Hence, MALAT1 could upregulate the HOXC4 by binding to miR-608. The suppressed progression of uveal melanoma in vitro by miR-608 was rescued by overexpression of MALAT1. Additionally, in vivo assays demonstrated that downregulation of MALAT1 could suppress tumor growth through downregulation of HOXC4 expression via increasing miR-608 in uveal melanoma. In summary, MALAT1 downregulation functions to restrain the development of uveal melanoma via miR-608-mediated inhibition of HOXC4.
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Long noncoding RNAs (lncRNAs) are emerging as key regulators of genetic and epigenetic networks, and their deregulation may underlie complex diseases, such as carcinogenesis. Several studies described lncRNA alterations in patients with solid tumors. In particular, HOTAIR upregulation has been associated with tumor aggressiveness, metastasis, and poor survival in gastrointestinal stromal tumor (GIST) patients. We analyzed expression levels of other lncRNAs, H19 and MALAT1, in FFPE tissue specimens from 40 surgically resected and metastatic GIST patients, using real-time PCR analysis. H19 and MALAT1 were both upregulated in 50% of GIST patients. MALAT1 lncRNA expression levels seem to be correlated with c-KIT mutation status. The percentage of both H19 and MALAT1 upregulation was significantly higher in patients with time to progression (TTP) < 6 months as compared to patients with TTP > 6 months. The median TTP was significantly lower in patients with both H19 and MALAT1 lncRNA upregulation as compared to those with lncRNA downregulation. These data suggest a potential role for both H19 and MALAT1 lncRNAs as prognostic biomarker for the clinical selection of the best candidate to first-line treatment with imatinib.
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Increasing evidences suggest that long noncoding RNAs (lncRNAs) play critical roles in the pathogenesis of coronary artery disease (CAD). However, the association between lncRNAs expression profiles and unstable angina (UA) remained poorly known. Thus, the present study aims to investigate expression patterns, biological functions, and diagnostic value of lncRNAs in UA.The present study explored the lncRNA and mRNA expression profiles in peripheral blood mononuclear cells (PBMCs) of UA patients and normal coronary artery (NCA) controls using RNA-seq. The biological function of differentially expressed lncRNAs was analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The expression of the selected lncRNAs was validated in another 44 UA patients and 46 NCA controls. Receiver operating characteristic curve (ROC) was performed to evaluate the diagnostic value of lncRNAs for UA.A total of 98 lncRNAs and 615 mRNAs were observed differentially expressed in PBMCs of UA patients as compared to NCA controls. The 10 most upregulated lncRNAs were LNC_000226, DANCR, RP1-167A14.2, LNC_002091, LNC_001526, LNC_001165, LNC_002772, LNC_000088, LNC_001226, and FAM157C, and the 10 most downregulated lncRNAs were RP11-734I18.1, RP11-185E8.1, RP11-360I2.1, LNC_001302, LNC_001287, RN7SL471P, LNC_000914, LINC01506, RP11-160E2.6, and LNC_000995. LNC_000226 and MALAT1 have high area under the curve values (AUC) for distinguishing UA from NCA patients (0.810 and 0.799, respectively), and the combination of MALAT1 and LNC_000226 increased the AUC value to 0.878.The present study added our understanding about the lncRNA expression profile in UA patients and provided potential biomarkers for the diagnosis of UA.
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In this study, we performed a comprehensive analysis of the transcriptome of one- and two-year-old male and female brains of Cynoglossus semilaevis by high-throughput Illumina sequencing. A total of 77,066 transcripts, corresponding to 21,475 unigenes, were obtained with a N50 value of 4349 bp. Of these unigenes, 33 genes were found to have significant differential expression and potentially associated with growth, from which 18 genes were down-regulated and 12 genes were up-regulated in two-year-old males, most of these genes had no significant differences in expression among one-year-old males and females and two-year-old females. A similar analysis was conducted to look for genes associated with reproduction; 25 genes were identified, among them, five genes were found to be down regulated and 20 genes up regulated in two-year-old males, again, most of the genes had no significant expression differences among the other three. The performance of up regulated genes in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was significantly different between two-year-old males and females. Males had a high gene expression in genetic information processing, while female’s highly expressed genes were mainly enriched on organismal systems. Our work identified a set of sex-biased genes potentially associated with growth and reproduction that might be the candidate factors affecting sexual dimorphism of tongue sole, laying the foundation to understand the complex process of sex determination of this economic valuable species.
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Emerging evidence suggests that anthocyanins prevent type 2 diabetes (T2D), however, its mechanisms remain elusive. Herein, we sought to elucidate the antihyperglycemic mechanism of pelargonidin-3-O-glucoside (Pg3G) extracted from wild raspberry based on RNA-sequence. Our study showed that Pg3G ameliorated glucose intolerance and insulin resistance in db/db mice. Besides, Pg3G improved serum lipid profiles and attenuated hepatic dysfunction. RNA-sequence analysis showed that Pg3G contributed to 301 genes upregulated and 269 genes downregulated. Further GO, KEGG and GSEA analysis indicated that Pg3G led to differential gene expressions enriched in glucose and lipid metabolism by upregulation of Elovl7, C1ql3, Cybb, Cytip, Src, Pdk4 and downregulation of Fasn, Aacs, Srebp1c, Mlxipl, Sorbs3, Gck, Slc2a4. RT-PCR validation of selected genes exhibited a positive correlation between RNA-sequence and RT-PCR results. Taken together, this study demonstrated that Pg3G attenuated T2D by regulating glucose and lipid metabolism, which implicates the potential for T2D therapeutics.
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Pecan (Carya illinoinensis) is an economically important nut tree that is greatly affected by drought, limiting its production and distribution. Although the complete genome of the pecan was published several years ago, the molecular basis of the pecan’s response to drought remains unclear. In this study, we analyzed the high-throughput transcriptome data for pecans under 3, 6, 9, 12, and 15 days of drought stress compared with the controls. A total of 12,893 differentially expressed genes (DEGs) were identified under drought stress, with 11,684 of them showing significant changes after 15 d of drought treatment. Among these, 4448 genes were up-regulated while 7226 were down-regulated. The trend analysis revealed that DEGs could be classified into 20 clusters. Surprisingly, the majority of genes (6148) showed a gradual down-regulation, and 3683 genes showed a gradual up-regulation in response to drought. Gene ontology enrichment analysis showed that the DEGs were mainly enriched in biological processes. The KEGG pathway enrichment results indicated that the DEGs were mainly enriched in several pathways, including metabolic pathways, the biosynthesis of secondary metabolites, and plant hormone signal transduction processes. Among the DEGs, 457 protein kinase and 734 transcription factor genes were shown to be drought-responsive and may play key roles in the response to drought, and the expression patterns of selected candidate genes were further validated using quantitative real-time PCR. Collectively, these findings highlighted the multiple processes in pecans under drought stress and provided valuable insights into the further investigation of the functions of drought stress-responsive genes and the molecular basis of the pecan drought stress response.
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Fat tail in sheep presents a valuable energy reserve that has historically facilitated adaptation to harsh environments. However, in modern intensive and semi-intensive sheep industry systems, breeds with leaner tails are more desirable. In the present study, RNA sequencing (RNA-Seq) was applied to determine the transcriptome profiles of tail fat tissues in two Chinese sheep breeds, fat-rumped Altay sheep and thin-tailed Xinjiang fine wool (XFW) sheep, with extreme fat tail phenotype difference. Then the differentially expressed genes (DEGs) and their sequence variations were further analyzed. In total, 21,527 genes were detected, among which 3,965 displayed significant expression variations in tail fat tissues of the two sheep breeds ( P < 0.05), including 707 upregulated and 3,258 downregulated genes. Gene Ontology (GO) analysis disclosed that 198 DEGs were related to fat metabolism. In Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the majority of DEGs were significantly enriched in “adipocytokine signaling,” “PPAR signaling,” and “metabolic pathways” ( P < 0.05); moreover, some genes were involved in multiple pathways. Among the 198 DEGs, 22 genes were markedly up- or downregulated in tail fat tissue of Altay sheep, indicating that these genes might be closely related to the fat tail trait of this breed. A total of 41,724 and 42,193 SNPs were detected in the transcriptomic data of tail fat tissues obtained from Altay and XFW sheep, respectively. The distribution of seven SNPs in the coding regions of the 22 candidate genes was further investigated in populations of three sheep breeds with distinct tail phenotypes. In particular, the g.18167532T/C (Oar_v3.1) mutation of the ATP-binding cassette transporter A1 ( ABCA1 ) gene and g.57036072G/T (Oar_v3.1) mutation of the solute carrier family 27 member 2 ( SLC27A2 ) gene showed significantly different distributions and were closely associated with tail phenotype ( P < 0.05). The present study provides transcriptomic evidence explaining the differences in fat- and thin-tailed sheep breeds and reveals numerous DEGs and SNPs associated with tail phenotype. Our data provide a valuable theoretical basis for selection of lean-tailed sheep breeds.
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Plants have developed several strategies for coping with phosphorus (P) deficiency. However, the details of the regulation of gene expression of adaptations to low P are still unclear. Using a cDNA microarray, transcriptomic analyses were carried out of the rice genes regulated by P deficiency and P re-supply to P-deficient plants. The OsPI1 gene, which was isolated as the most significant up-regulated gene under –P conditions, was also the most significant down-regulated gene following P re-supply. Many starch metabolism-related genes, as well as several genes for Pi-liberating enzymes, were up-regulated by –P treatment, suggesting a homeostatic contribution to the Pi concentration in leaf tissues. mRNAs for glucanases were also induced by P re-supply: these are suspected to play a role in loosening the cell wall compounds. Most of the genes up-regulated by –P treatment were down-regulated by P re-supply, suggesting that their responses were specific to –P conditions. Conversely, the number of genes up-regulated by P re-supply was also larger following P re-supply than in the –P condition. It is proposed that the genes up-regulated by P re-supply play an important role in P acquisition by P-deficient plants.
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The differentially expressed genes between glioblastoma (GBM) cells and normal human brain cells were investigated to performed pathway analysis and protein interaction network analysis for the differentially expressed genes. GSE12657 and GSE42656 gene chips, which contain gene expression profile of GBM were obtained from Gene Expression Omniub (GEO) database of National Center for Biotechnology Information (NCBI). The 'limma' data packet in 'R' software was used to analyze the differentially expressed genes in the two gene chips, and gene integration was performed using 'RobustRankAggreg' package. Finally, pheatmap software was used for heatmap analysis and Cytoscape, DAVID, STRING and KOBAS were used for protein-protein interaction, Gene Ontology (GO) and KEGG analyses. As results: i) 702 differentially expressed genes were identified in GSE12657, among those genes, 548 were significantly upregulated and 154 were significantly downregulated (p<0.01, fold-change >1), and 1,854 differentially expressed genes were identified in GSE42656, among the genes, 1,068 were significantly upregulated and 786 were significantly downregulated (p<0.01, fold-change >1). A total of 167 differentially expressed genes including 100 upregulated genes and 67 downregulated genes were identified after gene integration, and the genes showed significantly different expression levels in GBM compared with normal human brain cells (p<0.05). ii) Interactions between the protein products of 101 differentially expressed genes were identified using STRING and expression network was established. A key gene, called CALM3, was identified by Cytoscape software. iii) GO enrichment analysis showed that differentially expressed genes were mainly enriched in 'neurotransmitter:sodium symporter activity' and 'neurotransmitter transporter activity', which can affect the activity of neurotransmitter transportation. KEGG pathway analysis showed that the differentially expressed genes were mainly enriched in 'protein processing in endoplasmic reticulum', which can affect protein processing in endoplasmic reticulum. The results showed that: i) 167 differentially expressed genes were identified from two gene chips after integration; and ii) protein interaction network was established, and GO and KEGG pathway analyses were successfully performed to identify and annotate the key gene, which provide new insights for the studies on GBN at gene level.
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