scholarly journals Integrated Analysis of Competing Endogenous RNAs Network Reveals Potential Signatures in Osteosarcoma Development

2020 ◽  
Vol 19 ◽  
pp. 153303382095702
Author(s):  
Lisong Heng ◽  
Zhen Jia ◽  
Jian Sun ◽  
Yitong Zhao ◽  
Kun Zhang ◽  
...  

The purpose of this work was to extract key players such as mRNAs and long non-coding RNA (lncRNAs) in the etiopathogenesis of osteosarcoma (OS). The sequencing analyses (mRNAs and lncRNAs) of OS were conducted followed by differentially expressed mRNAs and lncRNAs (DEmRNAs and DElncRNAs) identification between U-2OS cells with has-miR-590-5p overexpression and negative control cells. Following this, the co-expression and functional enrichment analyses of DEmRNAs and DElncRNAs were carried out. Also, the miRNAs-DElncRNAs-DEmRNAs regulatory network was constructed with DElncRNAs-miRNAs and DElncRNAs-DEmRNAs pairs after the target gene analysis of miRNA. In addition, the ceRNA-has-miR-590-5p was further extracted based on the has-miR-590-5p-DElncRNAs and DElncRNAs-DEmRNAs interactions. Finally, the results of the bioinformatics analysis was verified by reverse-transcription polymerase chain reaction (RT-PCR). Totally, 980 DEmRNAs (539 up-regulated DEmRNAs and 441 down-regulated DEmRNAs) and 682 DElncRNAs (352 up-regulated DElncRNAs and 330 down-regulated DElncRNAs) were extracted between cells with hsa-miR-590-5p overexpression and normal cells. The functional analyses suggested that up-regulated genes were significantly enriched in several GO terms such as signal transduction and cytokine-cytokine receptor interaction pathway while down-regulated genes ( SCUBE3, HIST1H4E and EDIL3) were associated with calcium ion binding, cell surface function and nucleosome assembly. Additionally, the miRNAs-DEmRNAs-DEmRNAs network represented 220 pairs among 41 miRNAs, 38 DElncRNAs and 61 DEmRNAs. Furthermore, the ceRNA-hsa-miR-590-5p network consisted of 70 interaction pairs including hsa-miR-590-5p- SCUBE3-CTB-113D17.1, hsa-miR-590-5p- EDIL3-CTB-113D17.1 and hsa-miR-590-5p- HIST1H4E-CTB-113D17.1) among hsa-miR-590-5p, 30 DEmRNAs and 4 down-regulated DElncRNAs. Meanwhile, the RT-PCR results incidated that compared with the blank (KB) and negative control (NC) group, the mRNA expression of SCUBE3, HIST1H4E, and EDIL3 were significantly descreased in mimics group (P value <0.05). The lncRNA CTB-113D17.1 might implicate with OS development probably via serving as a hsa-miR-590-5p sponge to regulate gene targets ( SCUBE3, EDIL3 and HIST1H4E), which will facilitate the deep understandings of OS progression.

2021 ◽  
Vol 33 (2) ◽  
pp. 147
Author(s):  
M. Rabaglino ◽  
J. B.-M. Secher ◽  
P. Hyttel ◽  
H. Kadarmideen

In cattle, ovarian superovulation followed by invivo embryo collection and transfer (MOET), and the invitro production (IVP) of embryos are used all over the world to improve animal genetics. Application of MOET has resulted in the production of billions of healthy animals during the past 40 years, and IVP has evolved and given rise to significant numbers of calves during the past 10 years. Nevertheless, the use of MOET and IVP can affect the embryo epigenome, and therefore its transcriptome, before and after elongation, as shown by different studies. The integration of publicly available epigenome-transcriptome datasets generated by these studies could lead to a robust characterisation of the impacts of the application of MOET and IVP. The goal of this study was to integrate all publicly available data about MOET and IVP embryos to determine temporally differentially methylated regions (DMRs) and differentially expressed genes (DEGs) from blastocyst to elongation between IVP and MOET embryos. Datasets were downloaded from the Gene Expression Omnibus (GEO) database. Accession numbers were (1) for epigenomics: GSE69173, GSE97517, and GSE101895, plus one provided dataset from O’Doherty et al. (2018 BMC Genomics, 19, 438; https://doi.org/10.1186/s12864-018-4818-3), all hybridized to the EDMA platform GPL18384; (2) for transcriptomics: GSE12327, GSE21030, GSE24596, GSE24936, GSE27817, and GSE40101, all hybridized to the Affymetrix platform GPL2112. Both types of data were analysed with the limma package for R software, and functional enrichment analysis was done with the DAVID database. For DMRs, comparisons between IVP and MOET were made from spherical blastocysts (n=16 per group) on Day 7, to embryos on Day 15, specifically in the trophectoderm (TE) or embryonic disc (ED) regions (n=4 per region and per group). For DEGs, comparisons between IVP and MOET were made from spherical blastocysts (n=9 per group) to elongated blastocysts on Day 13 and embryos undergoing gastrulation on Day 16 (n=6 per group). Considering a P-value &lt;0.05 and fold-change &gt;2, there were 16 672 (TE) and 26 264 (ED) DMRs and 2236 DEGs that temporally differed between IVP and MOET. Most of the identified DMRs were found in intronic regions (around 36%) rather than exonic regions (8%). However, DMRs that were more methylated at IVP compared with MOET contained exons encoding for genes that enriched the Wnt signalling Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway in the ED, and focal adhesion and ECM-receptor interaction KEGG pathways (P&lt;0.05) in the TE. Accordingly, DEGs with lower expression in elongated embryos (Day 13 and Day 16) at IVP as opposed to MOET were mainly associated with these three pathways. In conclusion, this multi-omics analysis demonstrates that even when embryos are produced under different conditions and experiments, the main changes imposed by IVP affected genes involved in embryonic development and adhesion to the endometrium, which could explain the lower survival rates at IVP compared with MOET.


2021 ◽  
Author(s):  
Bincheng Tang ◽  
Shenqiang Hu ◽  
Qingyuan Ouyang ◽  
Tianhao Wu ◽  
Yao Lu ◽  
...  

Abstract Background All birds reproduce via internal fertilization, but only ~ 3% of male birds possess the external genitalia that allows for intromission. Waterfowl (e.g., duck and goose) are representatives of them, and the external genitalia development of male geese is directly related to mating ability. Notably, some male geese show abnormal external genitalia development during ontogenesis. However, until now little is known about the molecular mechanisms of the external genitalia development in goose. In the present study, comparative transcriptomic analyses were performed on the hypothalamus, pituitary gland, testis, and external genitalia isolated from the 245-day-old male Tianfu meat geese showing normal (NEGG, n = 3) and abnormal (AEGG, n = 3) external genitals in order to provide a better understanding of the mechanisms controlling the development of the external genitalia in aquatic bird species. Results There were 107, 284, 2192, and 1005 differentially expressed genes (DEGs) identified in the hypothalamus, pituitary gland, testis and external genitalia between NEGG and AEGG. Functional enrichment analysis indicated that the DEGs identified in the hypothalamus were mainly enriched in the ECM-receptor interaction pathway. The ECM-receptor interaction, focal adhesion, and neuroactive ligand-receptor interaction pathways were significantly enriched by the DEGs in the pituitary gland. In the testis, the DEGs were involved in the neuroactive ligand-receptor interaction, cell cycle, oocyte meiosis and purine metabolism. In the external genitalia, the DEGs were mainly involved in the metabolic, neuroactive ligand-receptor interaction and WNT signaling pathways. Additionally, through protein-protein interaction (PPI) network and co-expression network integrated analysis, fifteen genes involved in the neuroactive ligand-receptor interaction and WNT signaling pathways were identified, including KNG1, LPAR2, LPAR3, NPY, PLCB1, AVPR1B, GHSR, GRM3, HTR5A, FSHB, FSHR, WNT11, WNT5A, WIF1, and WNT7B, which are potentially crucial for the development of goose external genitalia. Conclusions To our knowledge, this study is the first comparing the hypothalamus, pituitary gland, testis, and external genitalia transcriptomes of male geese exhibiting normal and abnormal external genitals. Significantly, we identified the key DEGs involved in the neuroactive ligand-receptor interaction pathway which regulates the WNT signaling pathway through PLCB1 to control the development of male goose external genitalia.


2021 ◽  
Author(s):  
Yang Li ◽  
Jianmin Sun ◽  
Guodong Wang

Abstract Osteosarcopenia is a geriatric syndrome coexistence of osteoporosis and sarcopenia. However, the molecular mechanism underlying osteosarcopenia have not been fully elucidated. Differentially expressed genes (DEGs) for osteoporosis and sarcopenia were respectively identified by analyzing four expression datasets from the GEO. We extracted the gene expression datasets GSE56814 and GSE56815 for osteoporosis, GSE1428 and GSE8479 for sarcopenia. 133 co-expressed DEGs were included in osteoporosis and sarcopenia datasets. Furthermore, functional enrichment analyses and PPI network construction were performed to explore the potential biological function of the DEGs and identify hub genes. S100 protein binding (GO:0044548; p-value = 1.83E-06) and regulation of mRNA metabolic process (GO:1903311; p-value = 2.30E-05) were significantly enriched in gene ontology(GO) analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that salmonella infection (hsa05132; p-value = 1.05E-04) and AMPK signaling pathway (hsa04152; p-value = 2.18E-03) were significantly enriched. According to the results of PPI, we finally identified five most critical genes as the hub genes, including AKT1, ANXA2, VIM, S100A6 and S100A11. The integrated analysis will contribute to the understanding of comprehensive molecular changes in osteosarcopenia and the development of new target therapies.


2017 ◽  
Vol 95 (3) ◽  
pp. 1092 ◽  
Author(s):  
J. Sun ◽  
M. Xie ◽  
Z. Huang ◽  
H. Li ◽  
T. chen ◽  
...  

2020 ◽  
Vol 26 ◽  
Author(s):  
Abdulqader Fadhil Abed ◽  
Yazun Bashir Jarrar ◽  
Hamzeh J Al-Ameer ◽  
Wajdy Al-Awaida ◽  
Su-Jun Lee

Background: Oxandrolone is a synthetic testosterone analogue that is widely used among bodybuilders and athletes. However, oxandrolone causes male infertility. Recently, it was found that metformin reduces the risk of infertility associated with diabetes mellitus. Aim: This study aimed to investigate the protective effects of metformin against oxandrolone-induced infertility in male rats. Methods: Rats continuously received one of four treatments (n=7) over 14 days: control DMSO administration, oxandrolone administration, metformin administration, or co-administration of oxandrolone and metformin. Doses were equivalent to those used for human treatment. Subsequently, testicular and blood samples were collected for morphological, biochemical, and histological examination. In addition, gene expression of the testosterone synthesizing enzyme CYP11A1 was analyzed in the testes using RT-PCR. Results: Oxandrolone administration induced male infertility by significantly reducing relative weights of testes by 48%, sperm count by 82%, and serum testosterone levels by 96% (ANOVA, P value < 0.05). In addition, histological examination determined that oxandrolone caused spermatogenic arrest which was associated with 2-fold downregulation of testicular CYP11A1 gene expression. However, co-administration of metformin with oxandrolone significantly ameliorated toxicological alterations induced by oxandrolone exposure (ANOVA, P value < 0.05). Conclusion: Metformin administration protected against oxandrolone-induced infertility in male rats. Further clinical studies are needed to confirm the protective effect of metformin against oxandrolone-induced infertility among athletes.


Author(s):  
Sophie Edouard ◽  
Rita Jaafar ◽  
Nicolas Orain ◽  
Philippe Parola ◽  
Philippe Colson ◽  
...  

AbstractELISA and chemiluminescence serological assays for COVID-19 are currently incorporating only one or two SARS-CoV-2 antigens. We developed an automated Western immunoblotting as a complementary serologic assay for COVID-19. The JessTM Simple Western system, an automated capillary-based assay, was used, incorporating an inactivated SARS-CoV-2 lineage 20a strain as the source of antigen, and total immunoglobulins (IgG, IgM, IgA) detection. In total, 602 sera were tested including 223 from RT-PCR-confirmed COVID-19 patients, 76 from patients diagnosed with seasonal HCoVs and 303 from coronavirus-negative control sera. We also compared this assay with the EUROIMMUN® SARS-CoV-2 IgG ELISA kit. Among 223 sera obtained from RT-PCR-confirmed COVID-19 patients, 180/223 (81%) exhibited reactivity against the nucleocapsid and 70/223 (31%) against the spike protein. Nucleocapsid reactivity was further detected in 9/76 (14%) samples collected from patients diagnosed with seasonal HCoVs and in 15/303 (5%) coronavirus-negative control samples. In the subset of sera collected more than 2 weeks after the onset of symptoms, the sensitivity was 94% and the specificity 93%, the latter value probably reflecting cross-reactivity of SARS-CoV-2 with other coronaviruses. The automated Western immunoblotting presented a substantial agreement (90%) with the compared ELISA (Cohen’s Kappa=0.64). Automated Western immunoblotting may be used as a second line test to monitor exposure of people to HCoVs including SARS-CoV-2.


Animals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 2006
Author(s):  
Hongyu Liu ◽  
Ibrar Muhammad Khan ◽  
Huiqun Yin ◽  
Xinqi Zhou ◽  
Muhammad Rizwan ◽  
...  

The mRNAs and long non-coding RNAs axes are playing a vital role in the regulating of post-transcriptional gene expression. Thereby, elucidating the expression pattern of mRNAs and long non-coding RNAs underlying testis development is crucial. In this study, mRNA and long non-coding RNAs expression profiles were investigated in 3-month-old calves and 3-year-old mature bulls’ testes by total RNA sequencing. Additionally, during the gene level analysis, 21,250 mRNAs and 20,533 long non-coding RNAs were identified. As a result, 7908 long non-coding RNAs (p-adjust < 0.05) and 5122 mRNAs (p-adjust < 0.05) were significantly differentially expressed between the distinct age groups. In addition, gene ontology and biological pathway analyses revealed that the predicted target genes are enriched in the lysine degradation, cell cycle, propanoate metabolism, adherens junction and cell adhesion molecules pathways. Correspondingly, the RT-qPCR validation results showed a strong consistency with the sequencing data. The source genes for the mRNAs (CCDC83, DMRTC2, HSPA2, IQCG, PACRG, SPO11, EHHADH, SPP1, NSD2 and ACTN4) and the long non-coding RNAs (COX7A2, COX6B2, TRIM37, PRM2, INHBA, ERBB4, SDHA, ATP6VOA2, FGF9 and TCF21) were found to be actively associated with bull sexual maturity and spermatogenesis. This study provided a comprehensive catalog of long non-coding RNAs in the bovine testes and also offered useful resources for understanding the differences in sexual development caused by the changes in the mRNA and long non-coding RNA interaction expressions between the immature and mature stages.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Guangzhong Xu ◽  
Kai Li ◽  
Nengwei Zhang ◽  
Bin Zhu ◽  
Guosheng Feng

Background. Construction of the transcriptional regulatory network can provide additional clues on the regulatory mechanisms and therapeutic applications in gastric cancer.Methods. Gene expression profiles of gastric cancer were downloaded from GEO database for integrated analysis. All of DEGs were analyzed by GO enrichment and KEGG pathway enrichment. Transcription factors were further identified and then a global transcriptional regulatory network was constructed.Results. By integrated analysis of the six eligible datasets (340 cases and 43 controls), a bunch of 2327 DEGs were identified, including 2100 upregulated and 227 downregulated DEGs. Functional enrichment analysis of DEGs showed that digestion was a significantly enriched GO term for biological process. Moreover, there were two important enriched KEGG pathways: cell cycle and homologous recombination. Furthermore, a total of 70 differentially expressed TFs were identified and the transcriptional regulatory network was constructed, which consisted of 566 TF-target interactions. The top ten TFs regulating most downstream target genes were BRCA1, ARID3A, EHF, SOX10, ZNF263, FOXL1, FEV, GATA3, FOXC1, and FOXD1. Most of them were involved in the carcinogenesis of gastric cancer.Conclusion. The transcriptional regulatory network can help researchers to further clarify the underlying regulatory mechanisms of gastric cancer tumorigenesis.


Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831769756 ◽  
Author(s):  
Hui Shi ◽  
Jin Pu ◽  
Xiao-Li Zhou ◽  
Yun-Ye Ning ◽  
Chong Bai

This study aimed to investigate the effects of long non-coding RNA ROR (regulator of reprogramming) on cisplatin (DDP) resistance in patients with non-small-cell lung cancer by regulating PI3K/Akt/mTOR signaling pathway. Human cisplatin-resistant A549/DDP cell lines were selected and divided into control group, negative control group, si-ROR group, ROR over-expression group, Wortmannin group, and ROR over-expression + Wortmannin group. MTT assay was used to determine the optimum inhibitory concentration of DDP. Quantitative real-time polymerase chain reaction and western blotting were applied to detect expressions of long non-coding RNA ROR, PI3K, Akt, and mTOR. Colony-forming assay, scratch test, Transwell assay, and flow cytometry were conducted to detect cell proliferation, migration, invasion, and apoptosis, respectively. Tumor-formation assay was performed to detect the growth of transplanted tumors. Long non-coding RNA ROR expression was high in human A549/DDP cell lines. Compared with the control and negative control groups, the mRNA and protein expressions of PI3K, Akt, mTOR, and bcl-2 decreased, whereas the mRNA and protein expression of bax and the sensitivity of cells to DDP significantly increased. Cell proliferation, migration, and invasion abilities decreased in the si-ROR and Wortmannin groups. In comparison with control and negative control groups, the mRNA and protein expressions of PI3K, Akt, mTOR, and bcl-2 increased, whereas the mRNA and protein expressions of bax decreased, the sensitivity of cells to DDP significantly increased, and cell proliferation, migration, and invasion abilities decreased in the ROR over-expression group. For nude mice in tumor-formation assay, compared with control and negative control groups, the tumor weight was found to be lighter (1.03 ± 0.15) g, the protein expressions of PI3K, Akt, mTOR, and bcl-2 decreased, and the protein expression of bax increased in the si-ROR group. Long non-coding RNA ROR may affect the sensitivity of lung adenocarcinoma cells to DDP by targeting PI3K/Akt/mTOR signaling pathway.


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