The co-expression networks of differentially expressed RBPs with TFs and LncRNAs related to clinical TNM stages of cancers
Background RNA-binding proteins (RBPs) play important roles in cellular homeostasis by regulating the expression of thousands of transcripts, which have been reported to be involved in human tumorigenesis. Despite previous reports of the dysregulation of RBPs in cancers, the degree of dysregulation of RBPs in cancers and the intrinsic relevance between dysregulated RBPs and clinical TNM information remains unknown. Furthermore, the co-expressed networks of dysregulated RBPs with transcriptional factors and lncRNAs also require further investigation. Results Here, we firstly analyzed the deviations of expression levels of 1,542 RBPs from 20 cancer types and found that (1) RBPs are dysregulated in almost all 20 cancer types, especially in BLCA, COAD, READ, STAD, LUAD, LUSC and GBM with proportion of deviation larger than 300% compared with non-RBPs in normal tissues. (2) Up- and down-regulated RBPs also show opposed patterns of differential expression in cancers and normal tissues. In addition, down-regulated RBPs show a greater degree of dysregulated expression than up-regulated RBPs do. Secondly, we analyzed the intrinsic relevance between dysregulated RBPs and clinical TNM information and found that (3) Clinical TNM information for two cancer types—CHOL and KICH—is shown to be closely related to patterns of differentially expressed RBPs (DE RBPs) by co-expression cluster analysis. Thirdly, we identified ten key RBPs (seven down-regulated and three up-regulated) in CHOL and seven key RBPs (five down-regulated and two up-regulated) in KICH by analyzing co-expression correlation networks. Fourthly, we constructed the co-expression networks of key RBPs between 1,570 TFs and 4,147 lncRNAs for CHOL and KICH, respectively. Conclusions These results may provide an insight into the understanding of the functions of RBPs in human carcinogenesis. Furthermore, key RBPs and the co-expressed networks offer useful information for potential prognostic biomarkers and therapeutic targets for patients with cancers at the N and M stages in two cancer types CHOL and KICH.
Lian et al. (2019) The co-expression networks of differentially expressed RBPs with TFs and LncRNAs related to clinical TNM stages of cancers. PeerJ 7:e7696 https://doi.org/10.7717/peerj.7696
Characteristics and prognosis of pelvic Ewing sarcoma: a SEER population-based study
Background The pelvis is one of the primary sites of Ewing sarcoma (ES) and is associated with poorer prognoses than the extremities. Due to the rarity of this disease and limited data available, the prognostic factors of pelvic ES remain controversial. Thus, this study aimed to identify independent prognostic factors, and develop a nomogram for predicting survival rates in patients with pelvic ES. Methods Using data provided by the Surveillance, Epidemiology, and End Results (SEER) database, variables including age, sex, race, tumor size, tumor stage, surgery, and radiotherapy were analyzed using the Kaplan–Meier method and Cox proportional hazards regression. Based on the results of multivariate analyses, a nomogram was built to predict the overall survival (OS) of patients with pelvic ES. The performance of the nomogram was evaluated by the concordance index (C-index). Results A total of 267 cases diagnosed between 2004 and 2016 were included in the study. Univariate and multivariate analyses showed that patients who were younger, white, had a localized tumor stage, or underwent surgery were associated with improved prognoses, while no significant differences were observed in OS based on sex, tumor size, or radiotherapy. A nomogram was developed and the C-index was 0.728, indicating adequate performance for survival prediction. Conclusions Age, race, tumor stage, and surgery were identified as independent prognostic factors for the OS of pelvic ES. The nomogram developed in this study can individually predict 3- and 5-year OS in patients with pelvic ES.
Chen et al. (2019) Characteristics and prognosis of pelvic Ewing sarcoma: a SEER population-based study. PeerJ 7:e7710 https://doi.org/10.7717/peerj.7710
MYB transcription factors in alfalfa (Medicago sativa): genome-wide identification and expression analysis under abiotic stresses
Background Alfalfa is the most widely cultivated forage legume and one of the most economically valuable crops in the world. Its survival and production are often hampered by environmental changes. However, there are few studies on stress-resistance genes in alfalfa because of its incomplete genomic information and rare expression profile data. The MYB proteins are characterized by a highly conserved DNA-binding domain, which is large, functionally diverse, and represented in all eukaryotes. The role of MYB proteins in plant development is essential; they function in diverse biological processes, including stress and defense responses, and seed and floral development. Studies on the MYB gene family have been reported in several species, but they have not been comprehensively analyzed in alfalfa. Methods To identify more comprehensive MYB transcription factor family genes, the sequences of 168 Arabidopsis thaliana, 430 Glycine max, 185 Medicago truncatula, and 130 Oryza sativa MYB proteins were downloaded from the Plant Transcription Factor Database. These sequences were used as queries in a BLAST search against the M. sativa proteome sequences provided by the Noble Research Institute. Results In the present study, a total of 265 MsMYB proteins were obtained, including 50 R1-MYB, 186 R2R3-MYB, 26 R1R2R3-MYB, and three atypical-MYB proteins. These predicted MsMYB proteins were divided into 12 subgroups by phylogenetic analysis, and gene ontology (GO) analysis indicated that most of the MsMYB genes are involved in various biological processes. The expression profiles and quantitative real-time PCR analysis indicated that some MsMYB genes might play a crucial role in the response to abiotic stresses. Additionally, a total of 170 and 914 predicted protein–protein and protein-DNA interactions were obtained, respectively. The interactions between MsMYB043 and MSAD320162, MsMYB253 and MSAD320162, and MsMYB253 and MSAD308489 were confirmed by a yeast two-hybrid system. This work provides information on the MYB family in alfalfa that was previously lacking and might promote the cultivation of stress-resistant alfalfa.
Zhou et al. (2019) MYB transcription factors in alfalfa (Medicago sativa): genome-wide identification and expression analysis under abiotic stresses. PeerJ 7:e7714 https://doi.org/10.7717/peerj.7714
Ecological networks reveal contrasting patterns of bacterial and fungal communities in glacier-fed streams in Central Asia
Bacterial and fungal communities in biofilms are important components in driving biogeochemical processes in stream ecosystems. Previous studies have well documented the patterns of bacterial alpha diversity in stream biofilms in glacier-fed streams, where, however, beta diversity of the microbial communities has received much less attention especially considering both bacterial and fungal communities. A focus on beta diversity can provide insights into the mechanisms driving community changes associated to large environmental fluctuations and disturbances, such as in glacier-fed streams. Moreover, modularity of co-occurrence networks can reveal more ecological and evolutionary properties of microbial communities beyond taxonomic groups. Here, integrating beta diversity and co-occurrence approach, we explored the network topology and modularity of the bacterial and fungal communities with consideration of environmental variation in glacier-fed streams in Central Asia. Combining results from hydrological modeling and normalized difference of vegetation index, this study highlighted that hydrological variables and vegetation status are major variables determining the environmental heterogeneity of glacier-fed streams. Bacterial communities formed a more complex and connected network, while the fungal communities formed a more clustered network. Moreover, the strong interrelations among the taxonomic dissimilarities of bacterial community (BC) and modules suggest they had common processes in driving diversity and taxonomic compositions across the heterogeneous environment. In contrast, fungal community (FC) and modules generally showed distinct driving processes to each other. Moreover, bacterial and fungal communities also had different driving processes. Furthermore, the variation of BC and modules were strongly correlated with hydrological properties and vegetation status but not with nutrients, while FC and modules (except one module) were not associated with environmental variation. Our results suggest that bacterial and fungal communities had distinct mechanisms in structuring microbial networks, and environmental variation had strong influences on bacterial communities but not on fungal communities. The fungal communities have unique assembly mechanisms and physiological properties which might lead to their insensitive responses to environmental variations compared to bacterial communities. Overall, beyond alpha diversity in previous studies, these results add our knowledge that bacterial and fungal communities have contrasting assembly mechanisms and respond differently to environmental variation in glacier-fed streams.
Ren et al. (2019) Ecological networks reveal contrasting patterns of bacterial and fungal communities in glacier-fed streams in Central Asia. PeerJ 7:e7715 https://doi.org/10.7717/peerj.7715
Urine proteome changes in rats subcutaneously inoculated with approximately ten tumor cells
Background Biomarkers are changes associated with the disease. Urine is not subject to homeostatic control and therefore accumulates very early changes, making it an ideal biomarker source. Usually, we have performed urinary biomarker studies involving at least thousands of tumor cells. However, no tumor starts from a thousand tumor cells. We therefore examined urine proteome changes in rats subcutaneously inoculated with approximately ten tumor cells. Methods Here, we serially diluted Walker-256 carcinosarcoma cells to a concentration of 102/mL and subcutaneously inoculated 0.1 mL of these cells into nine rats. The urine proteomes on days 0, 13 and 21 were analyzed by liquid chromatography coupled with tandem mass spectrometry. Results Hierarchical clustering analysis showed that the urine proteome of each sample at three time points were clustered into three clusters, indicating the good consistency of these nine rats when inoculated with the same limited tumor cells. Differential proteins on days 13 and 21 were mainly associated with cell adhesion, autophagic cell death, changes in extracellular matrix organization, angiogenesis, and the pentose phosphate pathway. All of these enriched functional processes were reported to contribute to tumor progression and could not be enriched through random allocation analysis. Conclusions Our results indicated that (1) the urine proteome reflects changes associated with cancer even with only approximately ten tumor cells in the body and that (2) the urine proteome reflects pathophysiological changes in the body with extremely high sensitivity and provides potential for a very early screening process of clinical patients.
Wei et al. (2019) Urine proteome changes in rats subcutaneously inoculated with approximately ten tumor cells. PeerJ 7:e7717 https://doi.org/10.7717/peerj.7717
Effects of shokyo (Zingiberis Rhizoma) and kankyo (Zingiberis Processum Rhizoma) on prostaglandin E2 production in lipopolysaccharide-treated mouse macrophage RAW264.7 cells
We previously reported that shokyo and kankyo, which are water-extracted fractions of ginger, reduced LPS-induced PGE2 production in human gingival fibroblasts. In this study, we examined the effects of these herbs on LPS-treated mouse macrophage RAW264.7 cells. Both shokyo and kankyo reduced LPS-induced PGE2 production in a concentration-dependent manner. Shokyo and kankyo did not inhibit cyclooxygenase (COX) activity, nor did they alter the expression of molecules in the arachidonic acid cascade. In addition, these herbs did not alter NF-κB p65 translocation into nucleus, or phosphorylation of p65 or ERK. These results suggest that shokyo and kankyo inhibit cPLA2 activity. Although 6-shogaol produced similar results to those of shokyo and kankyo, the concentration of 6-shogaol required for the reduction of PGE2 production were higher than those of 6-shogaol in shokyo and kankyo. Therefore, several gingerols and shogaols other than 6-shogaol may play a role in the reduction of LPS-induced PGE2 production. Thus, 6-shogaol, and other gingerols and shogaols inhibit cPLA2 activity and reduce LPS-induced PGE2 production via a different mechanism from traditional anti-inflammatory drugs. Moreover, kampo medicines that contain shokyo or kankyo are considered to be effective for inflammatory diseases.
Ara et al. (2019) Effects of shokyo (Zingiberis Rhizoma) and kankyo (Zingiberis Processum Rhizoma) on prostaglandin E2 production in lipopolysaccharide-treated mouse macrophage RAW264.7 cells. PeerJ 7:e7725 https://doi.org/10.7717/peerj.7725
Identification of lncRNAs associated with lung squamous cell carcinoma prognosis in the competitive endogenous RNA network
Background Long noncoding RNAs (lncRNAs) play a role in the formation, development, and prognosis of various cancers. Our study aimed to identify prognostic-related lncRNAs in lung squamous cell carcinoma (LUSC), which may provide new perspectives for individualized treatment of patients. Materials and Methods The RNA sequencing (lncRNA, microRNA (miRNA), mRNA) data and clinical information related to LUSC were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed RNA sequences were used to construct the competitive endogenous RNA (ceRNA) network. In present study, we mainly used two prognostic verification methods, Cox analysis and survival analysis, to identify the prognostic relevance of specific lncRNAs and construct prognostic model of lncRNA. Results Datasets on 551 samples of lncRNA and mRNA and 523 miRNA samples were retrieved from the TCGA database. Analysis of the normal and LUSC samples identified 170 DElncRNAs, 331 DEmiRNAs, and 417 DEmRNAs differentially expressed RNAs. The ceRNA network contained 27 lncRNAs, 43 miRNAs, and 11 mRNAs. Furthermore, we identified seven specific lncRNAs (ERVH48-1, HCG9, SEC62-AS1, AC022148.1, LINC00460, C5orf17, LINC00261) as potential prognostic factors after correlation analysis, and five of the seven lncRNAs (AC022148.1, HCG9, LINC00460, C5orf17, LINC00261) constructed a prognostic model of LUSC. Conclusion In present study, we identified seven lncRNAs in the ceRNA network that are associated with potential prognosis in LUSC patients, and constructed a prognostic model of LUSC which can be used to assess the prognosis risk of clinical patients. Further biological experiments are needed to elucidate the specific molecular mechanisms underlying them.
Qi et al. (2019) Identification of lncRNAs associated with lung squamous cell carcinoma prognosis in the competitive endogenous RNA network. PeerJ 7:e7727 https://doi.org/10.7717/peerj.7727
Liver slice culture as a model for lipid metabolism in fish
Hepatic lipid metabolism is traditionally investigated in vitro using hepatocyte monocultures lacking the complex three-dimensional structure and interacting cell types essential liver function. Precision cut liver slice (PCLS) culture represents an alternative in vitro system, which benefits from retention of tissue architecture. Here, we present the first comprehensive evaluation of the PCLS method in fish (Atlantic salmon, Salmo salar L.) and validate it in the context of lipid metabolism using feeding trials, extensive transcriptomic data, and fatty acid measurements. We observe an initial period of post-slicing global transcriptome adjustment, which plateaued after 3 days in major metabolic pathways and stabilized through 9 days. PCLS fed alpha-linolenic acid (ALA) and insulin responded in a liver-like manner, increasing lipid biosynthesis gene expression. We identify interactions between insulin and ALA, where two PUFA biosynthesis genes that were induced by insulin or ALA alone, were highly down-regulated when insulin and ALA were combined. We also find that transcriptomic profiles of liver slices are exceedingly more similar to whole liver than hepatocyte monocultures, both for lipid metabolism and liver marker genes. PCLS culture opens new avenues for high throughput experimentation on the effect of “novel feed composition” and represent a promising new strategy for studying genotype-specific molecular features of metabolism.
Harvey et al. (2019) Liver slice culture as a model for lipid metabolism in fish. PeerJ 7:e7732 https://doi.org/10.7717/peerj.7732
Engrailed 1 overexpression as a potential prognostic marker in Lower Grade Glioma
Background Engrailed 1 (EN1), as a member of homeobox-containing transcription factors, participates in the development of the brain. High expressions of EN1 exist in various tumors. However, the role of EN1 in lower grade glioma (LGG) is still unknown. Methods Coefficients of Cox regression were examined by data mining among 13 cancer types using OncoLnc to validate EN1 expressions in LGG patients from The Cancer Genome Atlas database (TCGA). Bioinformatic analysis was performed by using R2 and the UCSC Xena browser based on the data from 273 glioma cases in GSE16011 from GEO datasets and 530 cases of LGG patients in TCGA. Cases in GSE16011 were divided into two groups according to IDH1 mutation status. Cases in TCGA-LGG were classified to subtypes according to histopathological results, IDH1 mutation status and 1p19q status. The Kaplan–Meier survival curves were performed to analyze the relationship between EN1 expressions and clinicopathological characteristics and survival time respectively. Results Cox regression results showed that LGG was ranked statistically first among 13 different cancer types according to the false discovery rate (FDR) correction. Results from GSE16011 showed that: glioma, LGG and LGG with IDH1 mutation patients with high EN1 expressions had significantly shorter 5, 10, and 15-year overall survival time (OS) (p < 0.001). Similar results from TCGA-LGG showed that LGG patients with high EN1 expressions had significantly shorter 15-year OS, irrespective of IDH1 mutation and 1p19q co-deletion (p < 0.001). The astrocytoma subgroup showed highest levels of EN1 expression and shortest 5, 10 and 15-year OS compared with oligoastrocytoma and oligodendroglioma (p < 0.05). Conclusion EN1 can be used as a prognostic marker in LGG patients, combined with IDH1 mutation and 1p19q co-deletion.
Zhu et al. (2019) Engrailed 1 overexpression as a potential prognostic marker in Lower Grade Glioma. PeerJ 7:e7414 https://doi.org/10.7717/peerj.7414
Seasonal and inter-annual community structure characteristics of zooplankton driven by water environment factors in a sub-lake of Lake Poyang, China
Background Sub-lakes are important for the maintenance of the ecosystem integrity of Lake Poyang, and zooplankton play an important role in its substance and energy flow. Methods A seasonal investigation of zooplankton was conducted in spring (April), summer (July), autumn (October) and winter (January of the following year) from 2012 to 2016 in a sub-lake of Lake Poyang. The aim of the present study was to understand the seasonal dynamics and interannual variation of zooplankton communities and their relationship to environmental factors. Results A total of 115 species were identified in all samples in the four years, which comprised of 87 Rotifera, 13 Cladocera and 15 Copepoda. Rotifera was the dominant group in terms of quantity, and its species richness and abundance were significantly higher when compared to Cladocera and Copepoda (P < 0.05), while Cladocera dominated in terms of biomass. The species richness of Rotifera exhibited a significant seasonal difference (P < 0.05). Both the density and biomass of zooplankton revealed significant seasonal differences (P < 0.05). In general, the density and biomass of zooplankton were higher in summer and autumn, when compared to winter and spring. Biodiversity indices were dramatically lower in spring than in the other seasons. The non-metric multidimensional scaling (NMDS) analysis suggested that these zooplankton communities can be divided into three groups: spring community, summer-autumn community, and winter community. The seasonal succession of zooplankton communities did not have interannual reproducibility. In high water level years, the dominant species of zooplankton (Cladocerans and Copepods) in the wet season had a lower density, and the result in low water level years was exactly the opposite. The redundancy analysis revealed that water temperature (WT), conductivity, pH and dissolved oxygen (DO) had significant effects on the zooplankton community. Conclusions The community structure of zooplankton has a significant seasonal pattern, but has no interannual repeatability. In high water level years, the dominant species of zooplankton (Cladocerans and Copepods) in the wet season had a lower density, and the result in low water level years was exactly the opposite. The density, biomass and diversity indices of zooplankton were significantly different in different seasons. The present study was helpful in the further understanding of the ecosystem stability of lakes connected with rivers, providing scientific guidance for the protection of lake wetlands.
Hu et al. (2019) Seasonal and inter-annual community structure characteristics of zooplankton driven by water environment factors in a sub-lake of Lake Poyang, China. PeerJ 7:e7590 https://doi.org/10.7717/peerj.7590