scholarly journals Early transcriptome changes induced by the Geminivirus C4 oncoprotein: setting the stage for oncogenesis

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Carl Michael Deom ◽  
Magdy S. Alabady ◽  
Li Yang

Abstract Background The Beet curly top virus C4 oncoprotein is a pathogenic determinant capable of inducing extensive developmental abnormalities. No studies to date have investigated how the transcriptional profiles differ between plants expressing or not expressing the C4 oncoprotein. Results We investigated early transcriptional changes in Arabidopsis associated with expression of the Beet curly top virus C4 protein that represent initial events in pathogenesis via a comparative transcriptional analysis of mRNAs and small RNAs. We identified 48 and 94 differentially expressed genes at 6- and 12-h post-induction versus control plants. These early time points were selected to focus on direct regulatory effects of C4 expression. Since previous evidence suggested that the C4 protein regulated the brassinosteroid (BR)-signaling pathway, differentially expressed genes could be divided into two groups: those responsive to alterations in the BR-signaling pathway and those uniquely responsive to C4. Early transcriptional changes that disrupted hormone homeostasis, 18 and 19 differentially expressed genes at both 6- and 12-hpi, respectively, were responsive to C4-induced regulation of the BR-signaling pathway. Other C4-induced differentially expressed genes appeared independent of the BR-signaling pathway at 12-hpi, including changes that could alter cell development (4 genes), cell wall homeostasis (5 genes), redox homeostasis (11 genes) and lipid transport (4 genes). Minimal effects were observed on expression of small RNAs. Conclusion This work identifies initial events in genetic regulation induced by a geminivirus C4 oncoprotein. We provide evidence suggesting the C4 protein regulates multiple regulatory pathways and provides valuable insights into the role of the C4 protein in regulating initial events in pathogenesis.

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xiao-hua Li ◽  
Fu-ling Chen ◽  
Hong-lin Shen

Abstract Background Bone disease causes short-term or long-term physical pain and disability. It is necessary to explore new drug for bone-related disease. This study aimed to explore the role and mechanism of Salidroside in promoting osteogenic differentiation of adipose-derived stromal cells (ADSCs). Methods ADSCs were isolated and treated with different dose of Salidroside. Cell count kit-8 (CCK-8) assay was performed to assess the cell viability of ADSCs. Then, ALP and ARS staining were conducted to assess the early and late osteogenic capacity of ADSCs, respectively. Then, differentially expressed genes were obtained by R software. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the differentially expressed genes were further analyzed. The expression of OCN, COL1A1, RUNX2, WNT3A, and β-catenin were measured by real-time PCR and Western blot analysis. Last, β-catenin was silenced by small interfering RNA. Results Salidroside significantly increased the ADSCs viability at a dose-response manner. Moreover, Salidroside enhanced osteogenic capacity of ADSCs, which are identified by enhanced ALP activity and calcium deposition. A total of 543 differentially expressed genes were identified between normal and Salidroside-treated ADSCs. Among these differentially expressed genes, 345 genes were upregulated and 198 genes were downregulated. Differentially expressed genes enriched in the Wnt/β-catenin signaling pathway. Western blot assay indicated that Salidroside enhanced the WNT3A and β-catenin expression. Silencing β-catenin partially reversed the promotion effects of Salidroside. PCR and Western blot results further confirmed these results. Conclusion Salidroside promoted osteogenic differentiation of ADSCs through Wnt/β-catenin signaling pathway.


Genes ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 82
Author(s):  
Yunxiao Wei ◽  
Guoliang Li ◽  
Shujiang Zhang ◽  
Shifan Zhang ◽  
Hui Zhang ◽  
...  

Allopolyploidy is an evolutionary and mechanistically intriguing process involving the reconciliation of two or more sets of diverged genomes and regulatory interactions, resulting in new phenotypes. In this study, we explored the gene expression patterns of eight F2 synthetic Brassica napus using RNA sequencing. We found that B. napus allopolyploid formation was accompanied by extensive changes in gene expression. A comparison between F2 and the parent shows a certain proportion of differentially expressed genes (DEG) and activation\silent gene, and the two genomes (female parent (AA)\male parent (CC) genomes) showed significant differences in response to whole-genome duplication (WGD); non-additively expressed genes represented a small portion, while Gene Ontology (GO) enrichment analysis showed that it played an important role in responding to WGD. Besides, genome-wide expression level dominance (ELD) was biased toward the AA genome, and the parental expression pattern of most genes showed a high degree of conservation. Moreover, gene expression showed differences among eight individuals and was consistent with the results of a cluster analysis of traits. Furthermore, the differential expression of waxy synthetic pathways and flowering pathway genes could explain the performance of traits. Collectively, gene expression of the newly formed allopolyploid changed dramatically, and this was different among the selfing offspring, which could be a prominent cause of the trait separation. Our data provide novel insights into the relationship between the expression of differentially expressed genes and trait segregation and provide clues into the evolution of allopolyploids.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Zeng-Hong Wu ◽  
Yun Tang ◽  
Hong Yu ◽  
Hua-Dong Li

AbstractBreast cancer (BC) affects the breast tissue and is the second most common cause of mortalities among women. Ferroptosis is an iron-dependent cell death mode that is characterized by intracellular accumulation of reactive oxygen species (ROS). We constructed a prognostic multigene signature based on ferroptosis-associated differentially expressed genes (DEGs). Moreover, we comprehensively analyzed the role of ferroptosis-associated miRNAs, lncRNAs, and immune responses. A total of 259 ferroptosis-related genes were extracted. KEGG function analysis of these genes revealed that they were mainly enriched in the HIF-1 signaling pathway, NOD-like receptor signaling pathway, central carbon metabolism in cancer, and PPAR signaling pathway. Fifteen differentially expressed genes (ALOX15, ALOX15B, ANO6, BRD4, CISD1, DRD5, FLT3, G6PD, IFNG, NGB, NOS2, PROM2, SLC1A4, SLC38A1, and TP63) were selected as independent prognostic factors for BC patients. Moreover, T cell functions, including the CCR score, immune checkpoint, cytolytic activity, HLA, inflammation promotion, para-inflammation, T cell co-stimulation, T cell co-inhibition, and type II INF responses were significantly different between the low-risk and high-risk groups of the TCGA cohort. Immune checkpoints between the two groups revealed that the expressions of PDCD-1 (PD-1), CTLA4, LAG3, TNFSF4/14, TNFRSF4/8/9/14/18/25, and IDO1/2 among others were significantly different. A total of 1185 ferroptosis-related lncRNAs and 219 ferroptosis-related miRNAs were also included in this study. From the online database, we identified novel ferroptosis-related biomarkers for breast cancer prognosis. The findings of this study provide new insights into the development of new reliable and accurate cancer treatment options.


2020 ◽  
Author(s):  
Xue Fan ◽  
Meng Li ◽  
Min Xiao ◽  
Cong Liu ◽  
Mingguo Xu

Abstract Background: Kawasaki disease (KD) leads to coronary artery damage and the etiology of KD is unknown. The present study was designed to explore the differentially expressed genes (DEGs) in KD serum-induced human coronary artery endothelial cells (HCAECs) by RNA-sequence (RNA-seq). Methods: HCAECs were stimulated with serum (15% (v/v)), which were collected from 20 healthy children and 20 KD patients, for 24 hours. DEGs were then detected and analyzed by RNA-seq and bioinformatics analysis. Results: The expression of SMAD1, SMAD6, CD34, CXCL1, PITX2, and APLN was validated by qPCR. 102 genes, 59 up-regulated and 43 down-regulated genes, were significantly differentially expressed in KD groups. GO enrichment analysis showed that DEGs were enriched in cellular response to cytokines, cytokine-mediated signaling pathway, and regulation of immune cells migration and chemotaxis. KEGG signaling pathway analysis showed that DEGs were mainly involved in cytokine−cytokine receptor interaction, chemokine signaling pathway, and TGF−β signaling pathway. Besides, the mRNA expression levels of SMAD1, SMAD6, CD34, CXCL1, and APLN in the KD group were significantly up-regulated compared with the normal group, whilePITX2 was significantly down-regulated. Conclusion: 102 DEGs in KD serum-induced HCAECs were identified, and six new targets were proposed as potential indicators of KD.


2020 ◽  
Author(s):  
Jing Liang ◽  
Xin Zhang ◽  
Wenjia Zhao

Abstract Background: Systemic lupus erythematosus (SLE) is a chronic immune connective tissue disease, which is common in women of childbearing age and easy to cause multiple organ inflammatory injury. The occurrence of prostate cancer is the result of multiple factors and genes, but we have little understanding of the mechanism involved. In this study, we deeply explored and analyzed the existing gene data in GEO database in order to find the key genes and new therapeutic targets of SLE.Results: The expression profile dataset of GDS4185, GDS4888, GDS4889 and GDS4890 containing 99 specimens, 42 cases of SLE patients and 57 cases of normal volunteers, were downloaded from the Gene Expression Omnibus (GEO) website. The differentially expressed genes (DEGs) in different tissues was analyzed by statistical hypothesis T test. The gene ontology (GO) enrichment analysis was carried out by the DAVID online tool. KEGG pathway annotation of DEGs was carried out by the KOBAS online computing database. The protein–protein interaction (PPI) networks of the DEGs were built from the STRING website and Cytoscape software. A total of 839 DEGs were calculated from the four GEO datasets. The GO and KEGG analysis indicated that the functions of DEGs mostly participated in the Osteoclast differentiation, HTLV-I infection, Measles, FoxO signaling pathway, Herpes simplex infection, Primary immunodeficiency, Jak-STAT signaling pathway. The following 14 closely related genes, HERC5, TP53, CDC20, GNB2, GNB4, PPP2R1A, GNAI2, PMCH, SOCS3, HERC6, STAT1, SOCS1, ISG15, IFIT3, were key nodes from the PPI network. These genes may have synergistic or indirect interactions with each other in the process of biological metabolism inducing the pathogenesis of SLE.Conclusion: Mining geo database has great scientific research value. In the future, scientific research must fully excavate a variety of database analysis methods. In this study, the screened candidate genes provide effective theoretical basis for the diagnosis, treatment, expected evaluation and related laboratory research of SLE, which are worthy of further experimental verification.


2021 ◽  
Author(s):  
Yihuang Lin ◽  
Jianwen Su ◽  
Yutian Wang ◽  
Daorong Xu ◽  
Xianrong Zhang ◽  
...  

To investigate the molecular pathogenesis of bone with osteomyelitis, we developed implant-associated osteomyelitis (IAOM) models in mice. An orthopedic stainless pin was surgically placed in the right femoral mid-shaft of mice followed by an inoculation of S. aureus into the medullary cavity. Typical characteristics of IAOM, like periosteal reaction and intra-osseous abscess, occurred by day 14 post-infection. By day 28 post-infection, necrotic abscess, sequestrum formation and deformity of the whole femur were observed. Transcriptional analysis identified 101 and 1,702 differentially expressed genes (DEGs) between groups by days 3 and 14 post-infection, respectively. Analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes revealed the enrichment of pathways in response to bacterium, receptor-ligand activity and chemokine signaling by day 3 post-infection. However, by day 14 post-infection, the enrichment switched to angiogenesis, positive regulation of cell motility and migration, skeletal system development and cytokine-cytokine receptor interaction. Furthermore, protein-protein interaction network analysis identified 4 cytokines (Il6, Cxcl10, IFN-γ and Cxcl9) associated with IAOM at an early stage of infection. Overall, as the pathological changes in this mouse model were consistent with those in human IAOM, our model may be used to investigate the mechanism and treatment of IAOM. Furthermore, the data of transcriptome sequencing and bioinformatic analysis will be an important resource for dissecting the molecular pathogenesis of bone with IAOM. Highlights 1. An implant-associated osteomyelitis (IAOM) mice model was developed. 2. The pathological changes in this mouse model were consistent with those in human IAOM. 3. 101 and 1,702 differentially expressed genes (DEGs) were identified between groups by days 3 and 14 post-infection, respectively. 4. Il6, Cxcl10, IFN-γ and Cxcl9 were screened out as the most important genes associated with early stage IAOM


2020 ◽  
Author(s):  
Jinsheng Wang ◽  
Yutao Wang ◽  
Lei Gao ◽  
Yuhua Zhao ◽  
Junhua Liu ◽  
...  

Abstract Background Glioblastoma (GBM) is the most aggressive and most lethal primary malignant brain tumor, the 5-year survival rate of which is less than 5%. Novel potential molecular and mechanism of GBM need to investigate.Materials and methods Microarray data of GSE15824 was downloaded from GEO. Differentially expressed genes and lncRNAs were screened by Limma package in R studio, and pathway enrichment analysis was performed by clusterprofiler package in R studio and IPA. The ceRNA mechanism was analyzed and predicted by several kinds of online public databases.ResultsThere were 567 differentially expressed genes and 121 differentially expressed lncRNAs in GBM. And differentially expressed genes were mainly enriched in Tuberculosis, Staphylococcus aureus infection, Systemic lupus erythematosus, Basal cell carcinoma, TGF-beta signaling pathway and p53 signaling pathway. Besides, Neuroinflammation signaling pathway, Role of NFAT in regulation of the immune response, and Dendritic cell maturation were significantly activated in GBM. According to the analysis of target miRNAs of SEM4D and OSER1-AS1, a possible ceRNA mechanism OSER1-AS1/hsa-miR-520h/SEMA4D axis was predicted in GBM.Conclusion Bioinformatics analysis was employed to analyze GSE15824 chip, and predict the potential mechanism. The results revealed that the ceRNA mechanism, OSER1-AS1/hsa-miR-520h/SEMA4D axis, might play a vital role in GBM.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Zhaoqin Wang ◽  
Yan Huang ◽  
Di Wang ◽  
Rumeng Wang ◽  
Kunshan Li ◽  
...  

Acupuncture and moxibustion have definite clinical effects on treating ulcerative colitis (UC), but their mechanism is still unclear. To investigate the molecular mechanisms, we applied herb-partitioned moxibustion or electroacupuncture at the Tianshu (ST25) points on UC rats and used RNA sequencing to identify molecular consequences. Male Sprague Dawley (SD) rats were divided into 6 groups randomly: the normal control (NC) group, the control + herb-partitioned moxibustion (NCHM) group, the control + electroacupuncture (NCEA) group, the model (UC) group, the model + herb-partitioned moxibustion (UCHM) group, and the model + electroacupuncture (UCEA) group. Compared to the UC group, HE staining in the UCHM group and UCEA group indicated that colitis was relieved, the histopathological score and MPO were both significantly reduced, and the serum hs-CRP concentration was decreased significantly. The results of RNA-seq suggested that, compared to the NC group, 206 upregulated genes and 167 downregulated genes were identified in colon tissues from the UC group; compared to the UC group, the expression levels of some genes were both affected in the UCHM group and the UCEA group (684 differentially expressed genes were identified in the UCHM group, and 1182 differentially expressed genes were identified in the UCEA group). KEGG signal pathway analysis indicated that the differentially expressed genes in the UCHM group were associated with the JAK-STAT signaling pathway and cell adhesion molecule (CAM); the differentially expressed genes in the UCEA group were associated with the NF-κB signaling pathway, the toll-like receptor signaling pathways, the PI3K-Akt signaling pathway, the MAPK signaling pathway, and the Wnt signaling pathway. This is the first study to reveal the gene expression characteristics of the anti-inflammatory effect of UC rats from the perspective of acupuncture and moxibustion control, which provide a clue for further investigation into the molecular mechanisms of UC treatment by acupuncture and moxibustion.


2020 ◽  
Author(s):  
Yuanxiang Lu ◽  
Wensen Li ◽  
Ge Liu ◽  
Erwei Xiao ◽  
Senmao Mu ◽  
...  

Abstract Background: Duodenal papilla carcinoma (DPC) is a rare malignancy of the gastrointestinal tract with high recurrence rate, and the pathogenesis of this highly malignant neoplasm is yet to be fully elucidated. This study aims to identify key genes to further understand the biology and pathogenesis underlying the molecular alterations driving DPC, which could be potential diagnostic or therapeutic targets.Methods: Tumor samples of three DPC patients were collected and integrating RNA-seq analysis of tumor tissues and matched normal tissues were performed to discover differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were carried out to understand the potential bio-functions of the DPC differentially expressed genes (DEGs) and protein–protein interaction (PPI) network was constructed for functional modules analysis and dentification of hub genes. Results: A total of 110 DEGs were identified from our RNA-Seq data, GO and KEGG analyses showed that the DEGs were mainly enriched in multiple cancer-related functions and pathways, such as cell proliferation, IL-17signaling pathway, Jak-STAT signaling pathway, PPAR signaling pathway. The PPI network screened out six hub genes including IL-6, LEP, LCN2, CCND1, FABP4 and MMP1, which were identified as core genes in the network and potential therapeutic targets of DPC. Discussion: The current study provides new insight into the exploration of DPC pathogenesis and the screened hub genes may serve as potential diagnostic indicator and novel therapeutic target.


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