scholarly journals Comprehensive Analysis of Differences of N6-Methyladenosine of Lncrnas Between Atrazine-Inducedand Normal Xenopus Laevis Testis

2021 ◽  
Author(s):  
Xuejie Qi ◽  
Xiao Geng ◽  
Juan Zhang ◽  
Ling Li ◽  
Qiang Jia ◽  
...  

Abstract Background: Increasing evidence suggested N6-methyladenosine (m6A) plays an important role in RNA stability, degradation, splicing and translation. M6A is found in different RNA including long non-coding RNA (lncRNA) which has been found possess significant biological functions. Our previous study examined the m6A profile of mRNAs in testis tissues of Xenopus laevis (X. laevis) with and without treatment with 100 µg/L atrazine (AZ). The result revealed that m6A is a highly conserved modification across the species. Methods: In this study, we apply previous approach to further investigate m6A modification profile of lncRNAs and predict the potential mechanism. In brief, m6A was sequenced by MeRIP sequencing using the latest Illumina HiSeq sequencer. Pathway enrichment analysis was used to maps genes to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Results: The results showed that m6A of lncRNAs enriched around intergenic region in testes of X. laevis. We further investigated the differential expression of lncRNAs m6A in testes of AZ-exposed compared with that in animals from control group. The results indicated that up to 198 differentially methylated m6A sites were detected within 188 lncRNAs, in which 89 sites were significantly up-regulated and 109 sites were significantly down-regulated. Data from Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that AZ-affected lncRNAs m6A sites were mainly involved in 10 pathways in which 3 mutual pathways were found in the result of differentially m6A-methylated mRNAs. Conclusions: These findings suggest that differentially m6A-methylated lncRNAs and these 3 pathways may act on regulatory roles in abnormal testis development of AZ-exposed X. laevis. This study for the first time provide insights into the profile of lncRNAs m6A modifications in amphibian species.

Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 631
Author(s):  
Zhicheng Sun ◽  
Fangrui Lou ◽  
Yuan Zhang ◽  
Na Song

Acanthogobius ommaturus is a euryhaline fish widely distributed in coastal, bay and estuarine areas, showing a strong tolerance to salinity. In order to understand the mechanism of adaptation to salinity stress, RNA-seq was used to compare the transcriptome responses of Acanthogobius ommaturus to the changes of salinity. Four salinity gradients, 0 psu, 15 psu (control), 30 psu and 45 psu were set to conduct the experiment. In total, 131,225 unigenes were obtained from the gill tissue of A. ommaturus using the Illumina HiSeq 2000 platform (San Diego, USA). Compared with the gene expression profile of the control group, 572 differentially expressed genes (DEGs) were screened, with 150 at 0 psu, 170 at 30 psu, and 252 at 45 psu. Additionally, among these DEGs, Gene Ontology (GO) analysis indicated that binding, metabolic processes and cellular processes were significantly enriched. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis detected 3, 5 and 8 pathways related to signal transduction, metabolism, digestive and endocrine systems at 0 psu, 30 psu and 45 psu, respectively. Based on GO enrichment analysis and manual literature searches, the results of the present study indicated that A. ommaturus mainly responded to energy metabolism, ion transport and signal transduction to resist the damage caused by salinity stress. Eight DEGs were randomly selected for further validation by quantitative real-time PCR (qRT-PCR) and the results were consistent with the RNA-seq data.


2021 ◽  
Vol 43 (1) ◽  
Author(s):  
Xuejie Qi ◽  
Xiao Geng ◽  
Juan Zhang ◽  
Binpeng Qu ◽  
Xin Zhang ◽  
...  

Abstract Background Increasing evidence suggested N6-methyladenosine (m6A) modification is crucial for male germline development. However, m6A modification of lncRNAs gains a little attention in amphibians in recent years. Xenopus laevis (X. laevis) was chosen to be an ideal model organism for testing environmental endocrine disrupting chemicals (EDCs) exposure and resultant effects. Atrazine (AZ) as an endocrine disrupt can effect development of testis in amphibians. Our previous study revealed that m6A is a highly conserved modification across the species. Results The results of m6A sequences showed that m6A-methylated lncRNAs enriched in intergenic region in testes of X. laevis. We further examined the differential expression of lncRNAs m6A sites in testes of AZ-exposed and compared with that in animals from control group. The results indicated that up to 198 differentially methylated m6A sites were detected within 188 lncRNAs, in which 89 significantly up-methylated sites and 109 significantly down-methylated sites. Data from KEGG pathway analysis indicated that AZ-affected lncRNAs m6A sites were mainly involved in 10 pathways in which 3 mutual pathways were found in the result of differentially m6A-methylated mRNAs. Conclusions These findings suggested that differentially m6A-methylated lncRNAs and these 3 pathways may act on regulatory roles in abnormal testis development of AZ-exposed X. laevis. This study for the first time provides insights into the profile of lncRNAs m6A modifications in amphibian species.


2020 ◽  
Author(s):  
Lun Wu ◽  
Ying Wei ◽  
Wen-Bo Zhou ◽  
Jiao Zhou ◽  
Li-Hua Yang ◽  
...  

Abstract Background Borax, a boron compound, which is becoming widely recognized for its biological effects, including antioxidant activity, cytotoxicity, and potential therapeutic benefits. However, the specific molecular mechanisms underlying borax-induced anti-tumor effect still remain to be to further elucidated. MicroRNAs (miRNAs) may play key roles in cellular processes including tumor progression, cell apoptosis and cytotoxicity. Thus, this study aimed to investigate, whether miRNAs were involved in the borax-mediated anti-tumor effect using miRNA profiling of a human liver cancer cell line (HepG2) using gene-chip analysis.Methods Total RNA was extracted and purified from HepG2 cells that were treated with 4 mM borax for either 2 or 24 h. The samples underwent microarray analysis using an Agilent Human miRNA Array. Differentially expressed miRNAs were analysed by volcano plot and heatmap, and were validated using real-time fluorescent quantitative PCR (qPCR).ResultsAmong this, 2- or 24-h exposure to borax significantly altered the expression level of miRNAs in HepG2 cells, 4 or 14 were upregulated and 3 were downregulated compared with the control group, respectively (≥2-fold; P<0.05). GO enrichment analysis and KEGG pathway enrichment analysis revealed that target genes of differentially expressed miRNAs in HepG2 cells predominantly participated in MAPK signaling pathway, TGF-beta signaling pathway, NF-kappa B signaling pathway, etc; in 2-h borax treatment group, while Ras signaling pathway, FoxO signaling pathway, Cellular senescence, etc; involved in 24-h treatment group.Conclusions Result indicates that borax-induced anti-tumor effect may be associated with alterations in miRNAs.


2021 ◽  
Author(s):  
Fei Xie ◽  
Xue Jiang ◽  
Yang Yi ◽  
Zi-Jia Liu ◽  
Chen Ma ◽  
...  

Abstract The potential for preventive and therapeutic applications of H2 have now been confirmed in various disease. However, the effects of H2 on health status have not been fully elucidated. Our previous study reported changes in the body weight and 13 serum biochemical parameters during the six-month hydrogen intervention. To obtain a more comprehensive understanding of the effects of long-term hydrogen consumption, the plasma metabolome and gut microbiota were investigated in this study. Compared with the control group, 14 and 10 differential metabolites (DMs) were identified in hydrogen-rich water (HRW) and hydrogen inhalation (HI) group, respectively. Pathway enrichment analysis showed that HRW intake mainly affected starch and sucrose metabolism, and DMs in HI group were mainly enriched in arginine biosynthesis. 16S rRNA gene sequencing showed that HRW intake induced significant changes in the structure of gut microbiota, while no marked bacterial community differences was observed in HI group. HRW intake mainly induced significant increase in the abundance of Lactobacillus, Ruminococcus, Clostridium XI, and decrease in Bacteroides. HI mainly induced decreased abundances of Blautia and Paraprevotella. The results of this study provide basic data for further research on hydrogen medicine. Determination of the effects of hydrogen intervention on microbiota profiles could also shed light on identification of mechanism underlying the biological effects of molecular hydrogen.


2020 ◽  
Author(s):  
Kumari Sonal Choudhary ◽  
Eoin Fahy ◽  
Kevin Coakley ◽  
Manish Sud ◽  
Mano R Maurya ◽  
...  

ABSTRACTWith the advent of high throughput mass spectrometric methods, metabolomics has emerged as an essential area of research in biomedicine with the potential to provide deep biological insights into normal and diseased functions in physiology. However, to achieve the potential offered by metabolomics measures, there is a need for biologist-friendly integrative analysis tools that can transform data into mechanisms that relate to phenotypes. Here, we describe MetENP, an R package, and a user-friendly web application deployed at the Metabolomics Workbench site extending the metabolomics enrichment analysis to include species-specific pathway analysis, pathway enrichment scores, gene-enzyme information, and enzymatic activities of the significantly altered metabolites. MetENP provides a highly customizable workflow through various user-specified options and includes support for all metabolite species with available KEGG pathways. MetENPweb is a web application for calculating metabolite and pathway enrichment analysis.Availability and ImplementationThe MetENP package is freely available from Metabolomics Workbench GitHub: (https://github.com/metabolomicsworkbench/MetENP), the web application, is freely available at (https://www.metabolomicsworkbench.org/data/analyze.php)


2020 ◽  
Author(s):  
Jiali Xiong ◽  
Haojie Zhang ◽  
Bin Zeng ◽  
Jie Liu ◽  
Junyi Luo ◽  
...  

Abstract Background: The anterior pituitary is a key endocrine organ both in animal and human being drawing much concern. Exosomes are extracellular secretory vesicles carrying proteins, lipids and small RNAs. Previous studies have demonstrated that they had regulatory function both physiologically and pathologically. However, information on exosomes from anterior pituitary remains unknown.Results: In this study, we separated and identified exosomes from anterior pituitary of Duroc swine model for the first time. Total RNA was extracted and RNA-seq was performed, followed by a comprehensive analysis of miRNAs, lncRNAs and circRNAs. Resultantly, we obtained 343 known miRNAs and 73 novel miRNAs, 15545 lncRNAs and 494 circRNAs. Furthermore, GO and KEGG enrichment analysis showed that the ncRNAs in exosomes may participate in regulating intracellular signal transduction, cellular component organization or biogenesis, small molecule binding, transferase activity. The cross-talk between them also suggested that they may play an important role in signaling process and the biological regulation.Conclusions: This work firstly provides ncRNAs data in anterior pituitary exosomes from duroc swine breed. These results may serve as a fundamental resource for exploring the detailed functions of exosomes from anterior pituitary.


Author(s):  
Jiaqi Zhang ◽  
Hui Liu ◽  
Wenhao Zhang ◽  
Yinfang Li ◽  
Zhigang Fan ◽  
...  

Skin cutaneous melanoma (SKCM) is an aggressive form of skin cancer that results in high mortality rate worldwide. It is vital to discover effective prognostic biomarkers and therapeutic targets for the treatment of melanoma. Long non-coding RNA (lncRNA) has been verified to play an essential role in the regulation of gene expression in diseases and tumors. Therefore, it is significant to explore the function of lncRNAs in the development and progression of SKCM. In this paper, a set of differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were first screened out using 471 cutaneous melanoma samples and 813 normal skin samples. Gene Ontology and KEGG pathway enrichment analysis were performed to obtain the significant function annotations and pathways of DEmRNAs. We also ran survival analysis on both DElncRNAs and DEmRNAs to identify prognostic-related lncRNAs and mRNAs. Next, a set of hub genes derived from protein-protein interaction (PPI) network analysis and lncRNA target genes screened from starbase-ENCORI database were integrated to construct a lncRNA-mRNA regulatory module, which includes 6 lncRNAs 4 target mRNAs. We further checked the capacity of these lncRNA and mRNA in the diagnosis of melanoma, and found that single lncRNA can effectively distinguish tumor and normal tissue. Moreover, we ran CMap analysis to select a list of small molecule drugs for SKCM, such as EGFR inhibitor AG-490, growth factor receptor inhibitor GW-441756 and apoptosis stimulant betulinic-acid, which have shown therapeutic effect in the treatment of melanoma.


2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Chunli Piao ◽  
Qi Zhang ◽  
De Jin ◽  
Li Wang ◽  
Cheng Tang ◽  
...  

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. Owing to its complicated pathogenesis, no satisfactory treatment strategies for DN are available. Milkvetch Root is a common traditional Chinese medicine (TCM) and has been extensively used to treat DN in clinical practice in China for many years. However, due to the complexity of botanical ingredients, the exact pharmacological mechanism of Milkvetch Root in treating DN has not been completely elucidated. The aim of this study was to explore the active components and potential mechanism of Milkvetch Root by using a systems pharmacology approach. First, the components and targets of Milkvetch Root were analyzed by using the Traditional Chinese Medicine Systems Pharmacology database. We found the common targets of Milkvetch Root and DN constructed a protein-protein interaction (PPI) network using STRING and screened the key targets via topological analysis. Enrichment of Gene Ontology (GO) pathways and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed. Subsequently, major hubs were identified and imported to the Database for Annotation, Visualization and Integrated Discovery for pathway enrichment analysis. The binding activity and targets of the active components of Milkvetch Root were verified by using the molecular docking software SYBYL. Finally, we found 20 active components in Milkvetch Root. Moreover, the enrichment analysis of GO and KEGG pathways suggested that AGE-RAGE signaling pathway, HIF-1 signaling pathway, PI3K-Akt signaling pathway, and TNF signaling pathway might be the key pathways for the treatment of DN; more importantly, 10 putative targets of Milkvetch Root (AKT1, VEGFA, IL-6, PPARG, CCL2, NOS3, SERPINE1, CRP, ICAM1, and SLC2A) were identified to be of great significance in regulating these biological processes and pathways. This study provides an important scientific basis for further elucidating the mechanism of Milkvetch Root in treating DN.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yanhua Lv ◽  
Yanqing Liu ◽  
Yueqiang Wang ◽  
Fanrong Kong ◽  
Qiuxiang Pang ◽  
...  

Abstract Background This study aimed to explore the molecular mechanisms of tibolone treatment in postmenopausal women. Methods The gene set enrichment profile, GSE12446, which includes 9 human endometrial samples from postmenopausal women treated with tibolone (tibolone group) and 9 control samples (control group), was downloaded from GEO database for analysis. Differentially expressed genes (DEGs) in tibolone vs. control groups were identified and then used for function and pathway enrichment analysis. Protein–protein interaction (PPI) network and module analyses were also performed. Finally, drug–target interaction was predicted for genes in modules, and then were validated in Pubmed. Results A total of 238 up-regulated DEGs and 72 down-regulated DEGs were identified. These DEGs were mainly enriched in various biological processed and pathways, such as cilium movement (e.g., CCDC114 and DNAI2), calcium ion homeostasis, regulation of hormone levels and complement/coagulation cascades. PPI network contained 368 interactions and 166 genes, of which IGF1, DNALI1, CCDC114, TOP2A, DNAH5 and DNAI2 were the hue genes. A total of 96 drug–gene interactions were obtained, including 94 drugs and eight genes. TOP2A and HTR2B were found to be targets of 28 drugs and 38 drugs, respectively. Among the 94 obtained drugs, only 12 drugs were reported in studies, of which 7 drugs (e.g., epirubicin) were found to target TOP2A. Conclusions CCDC114 and DNAI2 might play important roles in tibolone-treated postmenopausal women via cilium movement function. TOP2A might be a crucial target of tibolone in endometrium of postmenopausal women.


2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 26-27
Author(s):  
Hannah Sweett ◽  
Murilo R Carvalho ◽  
Jose Felipe W Spricigo ◽  
Elvis Ticiani ◽  
Eduardo S Ribeiro ◽  
...  

Abstract Pregnancy failure in dairy cattle appears to be attributable to losses during embryogenesis, mainly within the first month. Models have estimated that pregnancies lost after day 30 of fertilization cost producers US $550/cow. The reasons for these losses are not well understood, and the transcriptome profile of the reproductive tract during the establishment of pregnancy may point to mechanisms. Thirty-eight cows in lactations 1 to 3 were artificially inseminated, and endometrial biopsies were collected on day 15 after artificial insemination to investigate the effect of parity on the preimplantation pregnancy outcome. Pregnancy status was determined by the presence of interferon-tau in the uterine flushing, revealing 19 pregnant (P) and 19 non-pregnant (NP) cows. Nineteen biopsy samples [9 cows in lactation 1 (6 P and 3 NP), 4 in lactation 2 (2 P and 2 NP), and 6 in lactation 3 (3P and 3NP)] with an average RNA integrity number of 7 were selected for RNA sequencing with an Illumina HiSeq analyzer. Sequence reads were assembled to the ARS_USD1.2.99 bovine reference genome using the CLC genomics workbench software. On average, the samples generated ~56 million reads and 94.99% were mapped to the reference genome. Differential gene expression analysis between P and NP cows identified 187, 60, and 136 differentially expressed genes (DEG) in lactation 1, 2 and 3, respectively (P &lt; 0.01, FDR &lt; 0.05, FC &gt; ±2). Metabolic pathway enrichment analysis identified several DEG upregulated in lactations 2 and 3 associated with IL-17 signaling pathway, although expression of IL-17 itself was not different. This pathway is part of the protective response against extracellular bacteria and likely participates in pregnancy maintenance through local regulation of immune function. Further functional genomic analyses will be performed to determine additional metabolic pathways, key regulator genes, and functional SNPs associated with the establishment of pregnancy.


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