scholarly journals Multi-Omics Characterization of Circular RNA-Encoded Novel Proteins Associated With Bladder Outlet Obstruction

2022 ◽  
Vol 9 ◽  
Author(s):  
Baoyi Zhu ◽  
Zhanfang Kang ◽  
Sihua Zhu ◽  
Yuying Zhang ◽  
Xiangmao Lai ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Quantitative Proteomics ◽  
Bladder Outlet Obstruction ◽  
Molecular Mechanisms ◽  
Outlet Obstruction ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Protein Profiles ◽  
Rt Pcr ◽  
Novel Proteins

Bladder outlet obstruction (BOO) is a common urologic disease associated with poorly understood molecular mechanisms. This study aimed to investigate the possible involvements of circRNAs (circular RNAs) and circRNA-encoded proteins in BOO development. The rat BOO model was established by the partial bladder outlet obstruction surgery. Differential expression of circRNA and protein profiles were characterized by deep RNA sequencing and iTRAQ quantitative proteomics respectively. Novel proteins encoded by circRNAs were predicted through ORF (open reading frame) selection using the GETORF software and verified by the mass spectrometry in proteomics, combined with the validation of their expressional alterations by quantitative RT-PCR. Totally 3,051 circRNAs were differentially expressed in bladder tissues of rat BOO model with widespread genomic distributions, including 1,414 up-regulated, and 1,637 down-regulated circRNAs. Our following quantitative proteomics revealed significant changes of 85 proteins in rat BOO model, which were enriched in multiple biological processes and signaling pathways such as the PPAR and Wnt pathways. Among them, 21 differentially expressed proteins were predicted to be encoded by circRNAs and showed consistent circRNA and protein levels in rat BOO model. The expression levels of five protein-encoding circRNAs were further validated by quantitative RT-PCR and mass spectrometry. The circRNA and protein profiles were substantially altered in rat BOO model, with great expressional changes of circRNA-encoded novel proteins.

scholarly journals Identification of Non-coding RNA Biomarkers in Stress-induced Depression via Comprehensive Analysis of Competing Endogenous RNA Network

2020 ◽  
Author(s):  
xuanjun liu ◽  
Lan Yan ◽  
Chun Lin ◽  
Yiliang Zhang ◽  
Haofei Miao ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Comprehensive Analysis ◽  
Differentially Expressed ◽  
Psychiatric Disease ◽  
Circular Rnas ◽  
Messenger Rnas ◽  
Competing Endogenous Rna ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Promising Perspective

Abstract BackgroundDepression is one of the most common psychiatric disease worldwide. Although the research about the pathogenesis of depression have achieved progress, the detailed effect of non-coding RNAs (ncRNAs) in depression are still not clearly elucidated. This study was aimed to identify non-coding RNA biomarkers in stress-induced depression via comprehensive analysis of competing endogenous RNA networkMethodsIn this present study, we acquired RNA expression from RNA seq expression profile in three mice with depressive-like behaviors using chronic restraint stress paradigm and three C57BL/6J wild-type mice as control mice. ResultsA total of 41 differentially expressed circular RNAs (circRNAs) and 181 differentially expressed messenger RNAs (mRNAs) were up-regulated, and 65 differentially expressed circRNAs and 289 differentially expressed mRNAs were down-regulated, which were selected by a threshold of fold change ≥2 and a p-value < 0.05. Gene Ontology was performed to analyze the biological functions, and we predicted potential signaling pathways based on Kyoto Encyclopedia of Genes and Genomes pathway database. In addition, we constructed a circRNA-microRNA (miRNA)-mRNA regulatory network to further identify non-coding RNAs biomarkers. ConclusionsOur findings provide a promising perspective for further research into molecular mechanisms of depression, and targeting circRNA -mediated competing endogenous RNA (ceRNA) network is a useful strategy to early recognize the depression.

scholarly journals RNA-Seq Profiling of Circular RNAs During Development of Hindgut in Rat Embryos With Ethylenethiourea-Induced Anorectal Malformations

2021 ◽  
Vol 12 ◽  
Author(s):  
Si Ying Li ◽  
Chen Yi Wang ◽  
Yun Xia Xiao ◽  
Xiao Bing Tang ◽  
Zheng Wei Yuan ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Quantitative Polymerase Chain Reaction ◽  
Anorectal Malformations ◽  
Normal Group ◽  
Differentially Expressed ◽  
Mitogen Activated Protein Kinase ◽  
Circular Rnas ◽  
Rna Seq ◽  
Pregnant Rats

Anorectal malformations (ARMs) are among the most common congenital terminal digestive tract malformations. Circular RNAs (circRNAs), a novel type of endogenous non-coding RNAs, play roles in the development of the digestive system; however, their contributions to the pathogenesis of ARMs are not well-established. In this study, we explored the mechanism underlying ethylenethiourea (ETU)-induced ARMs by profiling circRNA expression via RNA-seq and constructing a regulatory circRNA-miRNA-mRNA network. Nine pregnant rats were gavage-fed a single dose of 125 mg/kg 1% ETU (ARM group) on gestational day 10 (GD10), and another 9 pregnant rats received a similar dose of saline (normal group) as a control. Embryos were obtained by cesarean section on the key time-points of anorectal development (GD14, GD15, and GD16). Hindgut samples isolated from the fetuses were evaluated by high-throughput sequencing and differentially expressed circRNAs were validated by reverse transcription-quantitative polymerase chain reaction, agarose gel electrophoresis, and Sanger cloning and sequencing. A total of 18295 circRNAs were identified in the normal and ARM groups. Based on the 425 differentially expressed circRNAs (|Fc| &gt; 2, p &lt; 0.05), circRNA-miRNA and miRNA-mRNA pairs were predicted using miREAP, miRanda, and TargetScan. A total of 55 circRNAs (14 up- and 41 downregulated in the ARM group compared to the normal group) were predicted to bind to 195 miRNAs and 947 mRNAs. Competing endogenous RNA networks and a Kyoto Encyclopedia of Genes and Genomes analysis revealed that novel_circ_001042 had the greatest connectivity and was closely related to ARM-associated signaling pathways, such as the Wingless Type MMTV integration site family, mitogen-activated protein kinase, and transforming growth factor-β pathways. These results provide original insight into the roles of circRNAs in ARMs and provide a valuable resource for further analyses of molecular mechanisms and signaling networks.

scholarly journals Differentially Expressed Genes Correlated with Fibrosis in a Rat Model of Chronic Partial Bladder Outlet Obstruction

Processes ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 2219
Author(s):  
Yuan-Shuo Hsueh ◽  
Hui-Hua Chang ◽  
Shun-Yao Ko ◽  
Yi-Pai Lin ◽  
Wei-Yu Lin
Keyword(s):  
Differentially Expressed Genes ◽  
Rat Model ◽  
Bladder Outlet Obstruction ◽  
Outlet Obstruction ◽  
Clinical Problem ◽  
Differentially Expressed ◽  
Partial Bladder Outlet Obstruction ◽  
Bladder Weight ◽  
Gene Expression Alterations ◽  
Tgfb Signaling

Chronic partial bladder outlet obstruction (PBOO) is a prevalent clinical problem that may result from multiple etiologies. PBOO may be a secondary condition to various anatomical and functional abnormalities. Bladder fibrosis is the worst outcome of PBOO. However, gene alterations and the mechanism of fibrosis development after PBOO onset are not clear. Therefore, we aimed to investigate gene expression alterations during chronic PBOO. A rat model of PBOO was established and validated by a significant increase in rat bladder weight. The bladder samples were further analyzed by microarray, and differentially expressed genes (DEGs) that are more related to PBOO compared with the control genes were selected. The data showed that 16 significantly upregulated mRNAs and 3 significantly downregulated mRNAs are involved in fibrosis. Moreover, 13 significantly upregulated mRNAs and 12 significantly downregulated mRNAs are related to TGFB signaling. Twenty-two significantly upregulated mRNAs and nine significantly downregulated mRNAs are related to the extracellular matrix. The genes with differential expressions greater than four-fold included Grem1, Thbs1, Col8a1, Itga5, Tnc, Lox, Timp1, Col4a1, Col4a2, Bhlhe40, Itga1, Tgfb3, and Gadd45b. The gene with a differential expression less than a quarter-fold was Thbs2. These findings show the potential roles of these genes in the physiology of PBOO.

scholarly journals Testosterone and 17β-Estradiol Induce Glandular Prostatic Growth, Bladder Outlet Obstruction, and Voiding Dysfunction in Male Mice

Endocrinology ◽  
2012 ◽  
Vol 153 (11) ◽  
pp. 5556-5565 ◽  
Author(s):  
Tristan M. Nicholson ◽  
Emily A. Ricke ◽  
Paul C. Marker ◽  
Joseph M. Miano ◽  
Robert D. Mayer ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Bladder Outlet Obstruction ◽  
Lower Urinary Tract ◽  
Molecular Mechanisms ◽  
Voiding Dysfunction ◽  
Outlet Obstruction ◽  
Hormone Treatment ◽  
Male Mice ◽  
17Β Estradiol ◽  
Lower Urinary

Abstract Benign prostatic hyperplasia (BPH) and bladder outlet obstruction (BOO) are common in older men and can contribute to lower urinary tract symptoms that significantly impact quality of life. Few existing models of BOO and BPH use physiological levels of hormones associated with disease progression in humans in a genetically manipulable organism. We present a model of BPH and BOO induced in mice with testosterone (T) and 17β-estradiol (E2). Male mice were surgically implanted with slow-releasing sc pellets containing 25 mg T and 2.5 mg E2 (T+E2). After 2 and 4 months of hormone treatment, we evaluated voiding patterns and examined the gross morphology and histology of the bladder, urethra, and prostate. Mice treated with T+E2 developed significantly larger bladders than untreated mice, consistent with BOO. Some mice treated with T+E2 had complications in the form of bladder hypertrophy, diverticula, calculi, and eventual decompensation with hydronephrosis. Hormone treatment caused a significant decrease in the size of the urethral lumen, increased prostate mass, and increased number of prostatic ducts associated with the prostatic urethra, compared with untreated mice. Voiding dysfunction was observed in mice treated with T+E2, who exhibited droplet voiding pattern with significantly decreased void mass, shorter void duration, and fewer sustained voids. The constellation of lower urinary tract abnormalities, including BOO, enlarged prostates, and voiding dysfunction seen in male mice treated with T+E2 is consistent with BPH in men. This model is suitable for better understanding molecular mechanisms and for developing novel strategies to address BPH and BOO.

scholarly journals Molecular Mechanisms of Bladder Outlet Obstruction in Transgenic Male Mice Overexpressing Aromatase (Cyp19a1)

2011 ◽  
Vol 178 (3) ◽  
pp. 1233-1244 ◽  
Author(s):  
Wei Lin ◽  
Nafis A. Rahman ◽  
Jian Lin ◽  
Hua Zhang ◽  
Kemian Gou ◽  
...  
Keyword(s):  
Bladder Outlet Obstruction ◽  
Molecular Mechanisms ◽  
Outlet Obstruction ◽  
Male Mice ◽  
Transgenic Male

Microarray Analysis of Differentially Expressed microRNAs in Allergic Rhinitis

2011 ◽  
Vol 25 (6) ◽  
pp. e242-e246 ◽  
Author(s):  
Yu Shaoqing ◽  
Zhang Ruxin ◽  
Liu Guojun ◽  
Yan Zhiqiang ◽  
Hu Hua ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Microarray Analysis ◽  
Nasal Mucosa ◽  
Molecular Mechanisms ◽  
Protein Translation ◽  
Differentially Expressed ◽  
Common Disease ◽  
Rt Pcr ◽  
Mirna Microarray ◽  
Differentially Expressed Mirnas

Background Allergic rhinitis (AR) is a common disease characterized by chronic inflammation of the nasal mucosa, but we have not fully understood the mechanism responsible for the development of AR. MicroRNAs (miRNAs) are short endogenous noncoding RNAs regulating protein translation through a mechanism known as RNA interference. To understand the molecular mechanisms of miRNA involved in the pathogenesis of AR, expressed miRNAs in AR were investigated through genomewide microarray analysis. Methods Mammalian miRNA microarrays containing whole human mature and precursor miRNA sequences were used for analyzing eight samples of nasal mucosa of AR and eight samples of nonallergic patients. Quantitative reverse transcriptase–polymerase chain reaction (RT-PCR) of some different expressed miRNAs was used to confirm the array results. Results The miRNA microarray chip analysis identified 421 miRNAs differentially expressed in the nasal mucosa of AR, and a total of 9 miRNAs were identified in the AR group with twofold change compared with control samples (p < 0.05). These included up-regulated miRNAs, hsa-hsa-miR-7, and hsa-miRPlus-E1194, and down-regulated miRNAs, hsa-miR-498, hsa-miR-187, hsa-miR-874, hsa-miR-143, hsa-miR-886–3p, hsa-miR-224, and hsa-miR-767–5p. RT-PCR results also confirmed that part of differentially expressed miRNAs as hsa-miR-224, hsa-miR-187, and hsa-miR-143 were down-regulated in AR. Conclusion The report indicated that many miRNA expressions were altered in AR and differentially expressed miRNAs appear to be involved in the development of AR. The study of miRNAs may lead to a better understanding about the roles of identified miRNAs in the pathogenesis of AR; this would be considered in future therapeutic strategies.

scholarly journals Identification of circular RNAs in the ovarian follicles of Meishan and Duroc sows during the follicular phase

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Su Xie ◽  
Mengxun Li ◽  
Yansen Chen ◽  
Yi Liu ◽  
Lipeng Ma ◽  
...  
Keyword(s):  
Follicular Development ◽  
Ovarian Follicles ◽  
Follicular Phase ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Rna Seq ◽  
Rt Pcr ◽  
Reverse Transcription Pcr ◽  
New Perspective

Abstract Circular RNAs (circRNAs) are a newly discovered class of endogenous non-coding RNAs that play an important role in growth and development by regulating gene expression and participating in a variety of biological processes. However, the role of circRNAs in porcine follicles remains unclear. Therefore, this study examined middle-sized ovarian follicles obtained from Meishan and Duroc sows at day 4 of the follicular phase. High-throughput RNA sequencing (RNA-seq) was utilized to construct circRNAs, and differential expression was identified. The findings were validated using reverse transcription PCR (RT-PCR) and DNA sequencing, GO and KEGG analyses were performed, and potential miRNA targets were identified. The RNA-seq identified a total of 15,866 circRNAs, with 244 differentially expressed in the Meishan relative to the Duroc (111 up-regulated and 133 down-regulated). The RT-PCR finding confirmed the RNA-seq results, and quantitative real-time PCR (qPCR) analysis examining a subset of the circRNAs showed that they are resistant to RNase R digestion. Bioinformatics analysis (GO and KEGG) showed that the host genes associated with the differentially expressed circRNAs are involved in reproduction and follicular development signaling pathways. Furthermore, many of the circRNAs were found to interact with miRNAs that are associated with follicular development. This study presents a new perspective for studying circRNAs and provides a valuable resource for further examination into the potential roles of circRNAs in porcine follicular development.

5-Hydroxytryptamine-induced bladder hyperactivity via the 5-HT2A receptor in partial bladder outlet obstruction in rats

2013 ◽  
Vol 304 (7) ◽  
pp. F1020-F1027 ◽  
Author(s):  
Takumi Sakai ◽  
Ken-ichi Kasahara ◽  
Ken-ichi Tomita ◽  
Ichiro Ikegaki ◽  
Hiroshi Kuriyama
Keyword(s):  
Gene Expression ◽  
Bladder Outlet Obstruction ◽  
Smooth Muscles ◽  
Outlet Obstruction ◽  
Pcr Analysis ◽  
Receptor Subtypes ◽  
Rt Pcr ◽  
Contractile Responses ◽  
Partial Bladder Outlet Obstruction ◽  
Rat Bladder

We investigated the effects of partial bladder outlet obstruction (BOO) on the function and gene expression of 5-hydroxytryptamine (5-HT) receptor subtypes in rat bladder. Isometric contractions of the isolated bladders from sham-operated control and BOO rats were examined. The contractile responses to 5-HT were significantly increased in BOO rat bladder strips, while the responses to KCl, carbachol, or phenylephrine were not different from the control. The 5-HT-induced hypercontraction in BOO rat bladder strips was inhibited by ketanserin, a 5-HT2A receptor antagonist. The contractile responses to 5-HT in bladder strips were not affected by urothelium removal from the intact bladder. The gene expression of 5-HT receptor subtypes in the bladders was analyzed by RT-PCR. The mRNA expression of the 5-HT2A, 5-HT2B, 5-HT2C, 5-HT4, and 5-HT7 receptors was detected in both the control and BOO rat bladders. Quantitative RT-PCR analysis showed there was a significant increase of 5-HT2A receptor mRNA in the BOO rat bladder compared with the control bladder. On the other hand, the gene expression of the 5-HT4 receptor was not changed in the BOO rat bladder. These results suggest that the increased contractile responses to 5-HT in BOO rat bladder may be partly caused by 5-HT2A receptor upregulation in the detrusor smooth muscles.

scholarly journals Whole-Transcriptome Analysis of Preadipocyte and Adipocyte and Construction of Regulatory Networks to Investigate Lipid Metabolism in Sheep

2021 ◽  
Vol 12 ◽  
Author(s):  
Cheng Xiao ◽  
Tian Wei ◽  
Li Xiang Liu ◽  
Jian Qiang Liu ◽  
Chun Xin Wang ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Adipocyte Differentiation ◽  
Sequence Data ◽  
Differentially Expressed ◽  
Mitogen Activated Protein Kinase ◽  
Circular Rnas ◽  
Peroxisome Proliferator ◽  
Messenger Rnas ◽  
Whole Transcriptome

Many local sheep breeds in China have poor meat quality. Increasing intramuscular fat (IMF) content can significantly improve the quality of mutton. However, the molecular mechanisms of intramuscular adipocyte formation and differentiation remain unclear. This study compared differences between preadipocytes and mature adipocytes by whole-transcriptome sequencing and constructed systematically regulatory networks according to the relationship predicted among the differentially expressed RNAs (DERs). Sequencing results showed that in this process, there were 1,196, 754, 100, and 17 differentially expressed messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), respectively. Gene Ontology analysis showed that most DERs enriched in Cell Part, Cellular Process, Biological Regulation, and Binding terms. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that the DERs primarily focused on Focal adhesion, phosphoinositide 3-kinase (PI3K)-Akt, mitogen-activated protein kinase (MAPK), peroxisome proliferator-activated receptor (PPAR) signaling pathways. Forty (40) DERs were randomly selected from the core regulatory network to verify the accuracy of the sequence data. The results of qPCR showed that the DER expression trend was consistent with sequence data. Four novel promising candidate miRNAs (miR-336, miR-422, miR-578, and miR-722) played crucial roles in adipocyte differentiation, and they also participated in multiple and important regulatory networks. We verified the expression pattern of the miRNAs and related pathways’ members at five time points in the adipocyte differentiation process (0, 2, 4, 6, 8, 10 days) by qPCR, including miR-336/ACSL4/LncRNA-MSTRG71379/circRNA0002331, miR-422/FOXO4/LncRNA-MSTRG54995/circRNA0000520, miR-578/IGF1/LncRNA-MSTRG102235/circRNA0002971, and miR-722/PDK4/LncRNA-MSTRG107440/circ RNA0002909. In this study, our data provided plenty of valuable candidate DERs and regulatory networks for researching the molecular mechanisms of sheep adipocyte differentiation and will assist studies in improving the IMF.

scholarly journals Profiles and Bioinformatics Analysis of Differentially Expressed Circrnas in Taxol-Resistant Non-Small Cell Lung Cancer Cells

2018 ◽  
Vol 48 (5) ◽  
pp. 2046-2060 ◽  
Author(s):  
Ning Xu ◽  
Shaomu Chen ◽  
Yufeng Liu ◽  
Wei Li ◽  
Zeyi Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
A549 Cells ◽  
Small Cell ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Small Cell Lung

Background/Aims: Circular RNAs (circRNAs) act as microRNA (miRNA) sponges that regulate gene expression and are involved in physiological and pathological processes. In this study, we evaluated the roles of circRNAs in the chemoresistance of non-small cell lung cancer (NSCLC) to taxol. Methods: High-throughput circRNA microarrays were employed to investigate the circRNA profiles of parental A549 and taxol-resistant A549/Taxol cells. We predicted the miRNA targets of differentially expressed circRNAs via miRNA prediction software and then constructed a circRNA/miRNA network using Cytoscape. Bioinformatics analyses were performed to annotate dysregulated circRNAs in detail. Results: We detected 2909 significantly upregulated and 8372 downregulated circRNAs in A549/Taxol cells compared with A549 cells. The circRNA/miRNA network displayed their interactions, suggesting that circRNAs exert biological effects by absorbing and sequestering miRNA molecules. Computational Gene Ontology and pathway analyses were used to determine the biological function and signaling pathways of host genes of dysregulated circRNAs and to identify potential molecular mechanisms prompting the resistance of NSCLC to taxol. Conclusion: This study focusing on circRNAs related to taxol resistance provides a basis for clarifying the development and progression of drug resistance and for identifying therapeutic targets in NSCLC.

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