scholarly journals An RNA-seq-Based Expression Profiling of Radiation-Induced Esophageal Injury in a Rat Model

Dose-Response ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. 155932581984337 ◽  
Author(s):  
Zhiqiang Sun ◽  
Jinhui Li ◽  
Min Lin ◽  
Shuyu Zhang ◽  
Judong Luo ◽  
...  

Radiation-induced acute injury is the main reason for the suspension of radiotherapy and unsuccessful treatment of cancer. It is of great importance to understand the molecular mechanism of radiation-induced esophageal injury. We used RNA-seq data from normal esophageal tissue and irradiated esophageal tissues and applied computational approaches to identify and characterize differentially expressed genes and detected 40 059 messenger RNAs (mRNAs) previously annotated and 717 novel long noncoding RNAs (lncRNAs). There were 14 upregulated and 32 downregulated lncRNAs among the differentially expressed lncRNA group. Their target genes were involved in the mRNA surveillance pathway, pathological immune responses, and cellular homeostasis. Additionally, we found 853 differentially expressed mRNAs, and there were 384 upregulated and 469 downregulated mRNAs. Notably, we found that the differentially expressed mRNAs were enriched for steroid biosynthesis, the tumor necrosis factor signaling pathway, focal adhesion, pathways in cancer, extracellular matrix–receptor interaction, and so on. The response of normal esophageal tissues to ionizing radiation is multifarious. The radiation-induced cell damage response by multiple pathways followed by pathological immune responses activated. Studies on the dynamic network of molecules involved in radiation-induced esophageal injury are under way to clarify the regulatory mechanisms and identify the candidate targets.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tiankun Hui ◽  
Hongyang Jing ◽  
Xinsheng Lai

Abstract Background Neuromuscular junctions (NMJs) are chemical synapses formed between motor neurons and skeletal muscle fibers and are essential for controlling muscle contraction. NMJ dysfunction causes motor disorders, muscle wasting, and even breathing difficulties. Increasing evidence suggests that many NMJ disorders are closely related to alterations in specific gene products that are highly concentrated in the synaptic region of the muscle. However, many of these proteins are still undiscovered. Thus, screening for NMJ-specific proteins is essential for studying NMJ and the pathogenesis of NMJ diseases. Results In this study, synaptic regions (SRs) and nonsynaptic regions (NSRs) of diaphragm samples from newborn (P0) and adult (3-month-old) mice were used for RNA-seq. A total of 92 and 182 genes were identified as differentially expressed between the SR and NSR in newborn and adult mice, respectively. Meanwhile, a total of 1563 genes were identified as differentially expressed between the newborn SR and adult SR. Gene Ontology (GO) enrichment analyses, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and gene set enrichment analysis (GSEA) of the DEGs were performed. Protein–protein interaction (PPI) networks were constructed using STRING and Cytoscape. Further analysis identified some novel proteins and pathways that may be important for NMJ development, maintenance and maturation. Specifically, Sv2b, Ptgir, Gabrb3, P2rx3, Dlgap1 and Rims1 may play roles in NMJ development. Hcn1 may localize to the muscle membrane to regulate NMJ maintenance. Trim63, Fbxo32 and several Asb family proteins may regulate muscle developmental-related processes. Conclusion Here, we present a complete dataset describing the spatiotemporal transcriptome changes in synaptic genes and important synaptic pathways. The neuronal projection-related pathway, ion channel activity and neuroactive ligand-receptor interaction pathway are important for NMJ development. The myelination and voltage-gated ion channel activity pathway may be important for NMJ maintenance. These data will facilitate the understanding of the molecular mechanisms underlying the development and maintenance of NMJ and the pathogenesis of NMJ disorders.


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.


2019 ◽  
Vol 20 (12) ◽  
pp. 2855 ◽  
Author(s):  
Linyuan Shen ◽  
Mailin Gan ◽  
Qianzi Tang ◽  
Guoqing Tang ◽  
Yanzhi Jiang ◽  
...  

The biochemical and functional differences between oxidative and glycolytic muscles could affect human muscle health and animal meat quality. However, present understanding of the epigenetic regulation with respect to lncRNAs and circRNAs is rudimentary. Here, porcine oxidative and glycolytic skeletal muscles, which were at the growth curve inflection point, were sampled to survey variant global expression of lncRNAs and circRNAs using RNA-seq. A total of 4046 lncRNAs were identified, including 911 differentially expressed lncRNAs (p < 0.05). The cis-regulatory analysis identified target genes that were enriched for specific GO terms and pathways (p < 0.05), including the oxidation-reduction process, glycolytic process, and fatty acid metabolic. All these were closely related to different phenotypes between oxidative and glycolytic muscles. Additionally, 810 circRNAs were identified, of which 137 were differentially expressed (p < 0.05). Interestingly, some circRNA-miRNA-mRNA networks were found, which were closely linked to muscle fiber-type switching and mitochondria biogenesis in muscles. Furthermore, 44.69%, 39.19%, and 54.01% of differentially expressed mRNAs, lncRNAs, and circRNAs respectively were significantly enriched in pig quantitative trait loci (QTL) regions for growth and meat quality traits. This study reveals a mass of candidate lncRNAs and circRNAs involved in muscle physiological functions, which may improve understanding of muscle metabolism and development from an epigenetic perspective.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Candice P. Chu ◽  
Shiguang Liu ◽  
Wenping Song ◽  
Ethan Y. Xu ◽  
Mary B. Nabity

AbstractDogs with X-linked hereditary nephropathy (XLHN) are an animal model for Alport syndrome in humans and progressive chronic kidney disease (CKD). Using mRNA sequencing (mRNA-seq), we have characterized the gene expression profile affecting the progression of XLHN; however, the microRNA (miRNA, miR) expression remains unknown. With small RNA-seq and quantitative RT-PCR (qRT-PCR), we used 3 small RNA-seq analysis tools (QIAGEN OmicSoft Studio, miRDeep2, and CPSS 2.0) to profile differentially expressed renal miRNAs, top-ranked miRNA target genes, and enriched biological processes and pathways in CKD progression. Twenty-three kidney biopsies were collected from 5 dogs with XLHN and 4 age-matched, unaffected littermates at 3 clinical time points (T1: onset of proteinuria, T2: onset of azotemia, and T3: advanced azotemia). We identified up to 23 differentially expressed miRNAs at each clinical time point. Five miRNAs (miR-21, miR-146b, miR-802, miR-142, miR-147) were consistently upregulated in affected dogs. We identified miR-186 and miR-26b as effective reference miRNAs for qRT-PCR. This study applied small RNA-seq to identify differentially expressed miRNAs that might regulate critical pathways contributing to CKD progression in dogs with XLHN.


2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Jiahui Zhao ◽  
Shuyun Zhang ◽  
Liesong Chen ◽  
Xiaolong Liu ◽  
Haihong Su ◽  
...  

Abstract The toxic effects of ionizing radiation on the gonads have been widely recognized. Sphingosine 1-phosphate (S1P) has a protective effect on ovarian injury, and although it is known that mitochondria are involved in this process, the specific mechanism is not fully understood. The present study analysed the changes in the serum AMH and ovarian histology in Sprague-Dawley female rats exposed to X-ray radiation only or co-administered with S1P. The mRNA expression profile of ovarian tissue was further analysed via next-generation sequencing and bioinformatics approaches to screen out candidate mitochondria-related genes. Finally, differentially expressed target genes were verified by real-time PCR. The results showed that ionizing radiation could reduce the serum AMH level, destroy ovarian structure and decrease the number of follicles in rats, while S1P administration significantly attenuated the impairment of ovarian function. Gene ontology (GO) and KEGG pathway analysis revealed that a variety of genes related to mitochondrial function were differentially expressed, and the protective effect of S1P on mitochondria was more obvious in the acute phase 24 h after radiation. The differentially expressed mitochondrial function-related genes associated with the protective effect of S1P were UQCRH, MICU2 and GPX4, which were subsequently verified by RT-PCR. Therefore, ionizing radiation has a significant effect on ovarian function, and S1P has a protective effect on radiation-induced ovarian injury, in which mitochondria may play an important role. This study sheds new light on the mechanism of radiation-induced ovarian injury and helps develop a novel potential strategy to control it.


Animals ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1565
Author(s):  
Zhiyun Hao ◽  
Yuzhu Luo ◽  
Jiqing Wang ◽  
Jiang Hu ◽  
Xiu Liu ◽  
...  

Long non-coding RNAs (lncRNAs) are a kind of non-coding RNA with >200 nucleotides in length. Some lncRNAs have been proven to have clear regulatory functions in many biological processes of mammals. However, there have been no reports on the roles of lncRNAs in ovine mammary gland tissues. In the study, the expression profiles of lncRNAs were studied using RNA-Seq in mammary gland tissues from lactating Small-Tailed Han (STH) ewes and Gansu Alpine Merino (GAM) ewes with different milk yield and ingredients. A total of 1894 lncRNAs were found to be expressed. Compared with the GAM ewes, the expression levels of 31 lncRNAs were significantly up-regulated in the mammary gland tissues of STH ewes, while 37 lncRNAs were remarkably down-regulated. Gene Ontogeny (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that the target genes of differentially expressed lncRNAs were enriched in the development and proliferation of mammary epithelial cells, morphogenesis of mammary gland, ErbB signaling pathway, and Wnt signaling pathway. Some miRNA sponges of differentially expressed lncRNAs, reported to be associated with lactation and mammary gland morphogenesis, were found in a lncRNA-miRNA network. This study reveals comprehensive lncRNAs expression profiles in ovine mammary gland tissues, thereby providing a further understanding of the functions of lncRNAs in the lactation and mammary gland development of sheep.


2021 ◽  
Author(s):  
Biao Chen ◽  
Wenjie Fang ◽  
Yankai Li ◽  
Ting Xiong ◽  
Mingfang Zhou ◽  
...  

Ducks are an important source of meat and egg products for human beings. In China, duck breeding has gradually changed from the traditional floor-water combination system to multilayer cage breeding. Therefore, the present study collected the hypothalamus and pituitary of 113-day-old ducks after being caged for 3 days, in order to investigate the effect of cage-rearing on the birds. In addition, the same tissues (hypothalamus and pituitary) were collected from ducks raised in the floor-water combination system, for comparison. Thereafter, the transcriptomes were sequenced and the expression level of genes were compared. The results of sequencing analysis showed that a total of 506 and 342 genes were differentially expressed in the hy-po-thalamus and pituitary, respectively. Additionally, the differentially expressed genes were mainly enriched in signaling pathways involved in processing environmental information, including ECM-receptor interaction, neuroactive ligand-receptor interaction and focal adhesion. The findings also showed that there was a change in the alternative splicing of genes when ducks were transferred into the cage rearing system. However, there was no difference in the expression of some genes although there was a change in the expression of the isoforms of these genes. The findings herein can therefore help in understanding the mechanisms underlying the effect of caging on waterfowl. The results also highlight the gene regulatory networks involved in animal responses to acute stress.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Dionysios V Chartoumpekis ◽  
Panos Ziros ◽  
Ioannis Habeos ◽  
Venetsana Kyriazopoulou ◽  
Adam Smith ◽  
...  

Abstract Nrf2 (Nfe2l2) is a transcription factor that regulates a series of cytoprotective and antioxidant enzymes. Its cytoplasmic inhibitor Keap1 senses the presence of oxidative or electrophilic stress though the interaction of sulfhydryl groups of its cysteines with reactive species and ceases to bind Nrf2. Thus, Nrf2 can transfer to the nucleus and induce its target genes. Follicular thyroid cells have physiologically high levels of reactive oxygen species as oxidation of iodine is essential for iodination of thyroglobulin and thyroid hormones synthesis. We have shown previously that Nrf2 pathway is active in thyroid and regulates the transcription of thyroglobulin. We thus hypothesized that the response of thyroid to iodine excess should comprise Nrf2-dependent and -independent pathways. To this end, 3 months-old male C57Bl6J WT or Nrf2 knockout (KO) mice were exposed to 0.05% sodium iodide in their water for 7 days. Thyroids were excised and used for RNA extraction; RNA-seq was performed by Exiqon, with a fold-change cutoff set at 2. Selected representative genes of the enriched pathways were quantified by real-time qPCR to validate RNA-seq results. Pathway analysis of the differentially expressed genes was performed using the Ingenuity Pathway Analysis (IPA) software. Pathways that were enriched with a p-value&lt;0.05 were considered significant. 828 genes were differentially expressed in response to iodine exposure; 66% were upregulated, as were most of the highly enriched pathways (related to inflammatory-immune response, antioxidant response, xenobiotic metabolism, platelet activation and calcium signaling). About 300 genes were differentially expressed between WT and KO mice; highly enriched pathways were related to glutathione and xenobiotic metabolism, Ahr signaling and Nrf2 signaling and were all downregulated in KO mice. Analysis of the potential upstream regulators of these highly enriched pathways revealed that Nrf2 and NfkB are major regulators of the antioxidant and inflammatory response induction upon iodine exposure and that Tgfβ-Smad cascade regulates the induction of fibrosis signaling. Last, we performed an analysis limited to already known thyroid pathways. A few genes were enriched following this method; upregulation of Duoxa1 (hydrogen peroxide generator) and downregulation of Nis (sodium iodide symporter) upon iodine exposure, which are expected responses, and the downregulation of thyroglobulin and upregulation of Duoxa1 in KO mice that confirm our previous findings. In conclusion, Nrf2-driven cytoprotective response is upregulated after iodine overload along with induction of inflammatory pathways. Nrf2 regulates transcriptomic responses in the thyroid, including a small but significant part of the response to iodine challenge. Hence, Nrf2 can be considered a novel player in the frontiers of thyroid antioxidant response and thyroid economy.


Animals ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 1077 ◽  
Author(s):  
Chengchuang Song ◽  
Yongzhen Huang ◽  
Zhaoxin Yang ◽  
Yulin Ma ◽  
Buren Chaogetu ◽  
...  

In the beef industry, fat tissue is closely related to meat quality. In this study, high-throughput RNA sequencing was utilized for adipose tissue transcriptome analysis between cattle-yak, Qaidamford cattle, and Angus cattle. The screening and identification of differentially expressed genes (DEGs) between different breeds of cattle would facilitate cattle breeding. Compared to Angus cattle adipose tissue, a total of 4167 DEGs were identified in cattle-yak adipose tissue and 3269 DEGs were identified in Qaidamford cattle adipose tissue. Considering cattle-yak as a control group, 154 DEGs were identified in Qaidamford cattle adipose tissue. GO analysis indicated the significant enrichment of some DEGs related to lipid metabolism. The KEGG pathway database was also used to map DEGs and revealed that most annotated genes were involved in ECM-receptor interaction and the PI3K-Akt signal pathway, which are closely related to cell metabolism. Eight selected DEGs related to adipose tissue development or metabolism were verified by RT-qPCR, indicating the reliability of the RNA-seq data. The results of this comparative transcriptome analysis of adipose tissue and screening DEGs suggest several candidates for further investigations of meat quality in different cattle breeds.


2021 ◽  
Author(s):  
Zhou Chen ◽  
Hao Xu ◽  
Zhongtian Bai ◽  
Shi Dong ◽  
Jian Zhang ◽  
...  

Abstract Background Dysregulated expression of miRNAs in gastric cancer (GC) is associated with tumor progression. MiRNA markers are important for the prognosis and therapeutic targeting of GC patients. Methods To detect differentially expressed miRNAs in GC from the TCGA database and predict their target genes. We downloaded RNA sequencing (RNA-seq), miRNA-seq and clinical data of GC from TCGA. Differential expression analysis of RNA-seq and miRNA-seq data was performed by R 3.6.1. MiRNAs associated with prognosis were evaluated with the Cox model, and differentially expressed miRNAs were assessed by Kaplan–Meier curve analysis. Risk factors were identified in the Cox model. Target genes of differentially expressed miRNAs were searched in three databases. GO enrichment and KEGG pathway analyses were used to evaluate the biological functions of these target genes.Results Five miRNAs (hsa-miR-135b-3p, hsa-miR-143-5p, hsa-miR-196b-3p, hsa-miR-942-3p, hsa-miR-9-3p) were related to survival. Eight target genes (AKAP12, AR, DZIP1, PCDHA11, PCDHA12, PI15, SH3BGRL and TMEM108) were closely correlated with patient overall survival (OS). Conclusion Differentially expressed miRNAs and their target genes have an important influence on the diagnosis and prognosis of GC and may be used as tumor biomarkers in further studies and as potential therapeutic targets.


Sign in / Sign up

Export Citation Format

Share Document