Differential Expression Profiles and Functional Prediction of circRNAs in Necrotizing Enterocolitis

Circular RNAs (circRNAs), a novel type of noncoding RNAs, have been demonstrated to behave as microRNA (miRNA) sponges to exert their effects during pathological processes of diseases. However, the roles of circRNAs have not been explored in necrotizing enterocolitis (NEC). This study sought to identify differentially expressed circRNAs and predict their potential biological functions in NEC. circRNA expression profiles in terminal ileum from newborn rats with NEC and normal controls were explored using next-generation sequencing. In the NEC group, 53 circRNAs were significantly differentially expressed, including 9 upregulated and 44 downregulated. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted, and circRNA-miRNA interaction networks were generated to predict the potential roles of circRNAs in NEC progression. Further investigation revealed that most circRNAs include miRNA binding sites and that some are implicated in NEC development. In conclusion, this study’s findings demonstrate that differentially expressed circRNAs are involved in NEC development via their interactions with miRNAs, making them prospective targets for NEC diagnosis and treatment.

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Differential circular RNA expression profiles in umbilical cord blood exosomes from preeclampsia patients

BMC Pregnancy and Childbirth ◽

10.1186/s12884-021-03777-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Minkai Cao ◽

Juan Wen ◽

Chaozhi Bu ◽

Chunyan Li ◽

Yu Lin ◽

...

Keyword(s):

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Expression Profiles ◽

Circular Rna ◽

Circular Rnas ◽

Pathway Network ◽

Pathway Analyses ◽

Normal Controls

Abstract Background Exosomal circular RNAs (circRNAs) are emerging as important regulators of physiological development and disease pathogenesis. However, the roles of exosomal circRNAs from umbilical cord blood in preeclampsia (PE) occurrence remains poorly understood. Methods We used microarray technology to establish the differential circRNA expression profiles in umbilical cord blood exosomes from PE patients compared with normal controls. Bioinformatics analysis was conducted to further predict the potential effects of the differentially expressed circRNAs and their interactions with miRNAs. Results According to the microarray data, we identified 143 significantly up-regulated circRNAs and 161 significantly down-regulated circRNAs in umbilical cord blood exosomes of PE patients compared with controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analyses showed that circRNA parental genes involved in the regulation of metabolic process, trophoblast growth and invasion were significantly enriched, which play important roles in PE development. Moreover, pathway network was constructed to reveal the key pathways in PE, such as PI3K-Akt signaling pathway. Further circRNA/miRNA interactions analysis demonstrated that most exosomal circRNAs had miRNA binding sites, and some miRNAs were associated with PE. Conclusions Our results highlight the importance of exosomal circRNAs in the pathogenesis of PE and lay a foundation for extensive studies on the role of exosomal circRNAs in PE development.

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Differential Circular RNA Expression Profiles in Umbilical Cord Blood Exosomes from Preeclampsia Patients

10.21203/rs.3.rs-271818/v1 ◽

2021 ◽

Author(s):

Minkai Cao ◽

Juan Wen ◽

Chaozhi Bu ◽

Chunyan Li ◽

Yu Lin ◽

...

Keyword(s):

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Expression Profiles ◽

Circular Rna ◽

Circular Rnas ◽

Pathway Network ◽

Pathway Analyses ◽

Normal Controls

Abstract Exosomal circular RNAs (circRNAs) are emerging as important regulators of physiological development and disease pathogenesis. However, the roles of exosomal circRNAs from umbilical cord blood in preeclampsia (PE) occurrence remains poorly understood. In this study, we used microarray technology to establish the differential circRNA expression profiles in umbilical cord blood exosomes from PE patients compared with normal controls. According to the microarray data, we identified 143 significantly up-regulated circRNAs and 161 significantly down-regulated circRNAs in umbilical cord blood exosomes of PE patients compared with controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analyses demonstrated that circRNA parental genes involved in the regulation of metabolic process, trophoblast growth and invasion were significantly enriched, which are important in PE development. Moreover, pathway network was constructed to reveal the key pathways in PE, such as PI3K-Akt signaling pathway. Further circRNA/miRNA interactions analysis showed that most of the exosomal circRNAs harbored miRNA binding sites, and some miRNAs were associated with PE. Collectively, our results highlight the importance of exosomal circRNAs in the pathogenesis of PE and lay a foundation for extensive studies on the role of exosomal circRNAs in PE development.

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Comprehensive circRNA-microRNA-mRNA network analysis revealed the novel regulatory mechanism of Trichosporon asahii infection

Military Medical Research ◽

10.1186/s40779-021-00311-w ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Ming-Wang Zhang ◽

Zhi-Hong Zhu ◽

Zhi-Kuan Xia ◽

Xin Yang ◽

Wan-Ting Luo ◽

...

Keyword(s):

Signaling Pathway ◽

Noncoding Rna ◽

Expression Profiles ◽

Differentially Expressed ◽

Luciferase Reporter ◽

Circular Rnas ◽

Rna Seq ◽

Trichosporon Asahii ◽

Cerna Network ◽

Pathway Analyses

Abstract Background Invasive Trichosporon asahii (T. asahii) infection frequently occurs with a high mortality in immunodeficient hosts, but the pathogenesis of T. asahii infection remains elusive. Circular RNAs (circRNAs) are a type of endogenous noncoding RNA that participate in various disease processes. However, the mechanism of circRNAs in T. asahii infection remains completely unknown. Methods RNA sequencing (RNA-seq) was performed to analyze the expression profiles of circRNAs, microRNAs (miRNAs), and mRNAs in THP-1 cells infected with T. asahii or uninfected samples. Some of the RNA-seq results were verified by RT-qPCR. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to analyze the differentially expressed mRNAs. A circRNA-miRNA-mRNA network was constructed and verified by dual-luciferase reporter assay and overexpression experiments. Results A total of 46 circRNAs, 412 mRNAs and 47 miRNAs were differentially expressed at 12 h after T. asahii infection. GO and KEGG analyses showed that the differentially expressed mRNAs were primarily linked to the leukocyte migration involved in the inflammatory response, the Toll-like receptor signaling pathway, and the TNF signaling pathway. A competing endogenous RNA (ceRNA) network was constructed with 5 differentially expressed circRNAs, 5 differentially expressed miRNAs and 42 differentially expressed mRNAs. Among them, hsa_circ_0065336 was found to indirectly regulate PTPN11 expression by sponging miR-505-3p. Conclusions These data revealed a comprehensive circRNA-associated ceRNA network during T. asahii infection, thus providing new insights into the pathogenesis of the T. asahii-host interactions.

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The circular RNA circSlc7a11 promotes bone cancer pain pathogenesis in rats by modulating LLC-WRC 256 cell proliferation and apoptosis

Molecular and Cellular Biochemistry ◽

10.1007/s11010-020-04020-1 ◽

2021 ◽

Author(s):

Han-Wen Chen ◽

Xiao-Xia Zhang ◽

Zhu-Ding Peng ◽

Zu-Min Xing ◽

Yi-Wen Zhang ◽

...

Keyword(s):

Cell Proliferation ◽

Cancer Pain ◽

Expression Profiles ◽

Bone Cancer ◽

Circular Rna ◽

Differentially Expressed ◽

Bone Cancer Pain ◽

Circular Rnas ◽

Altered Expression ◽

Proliferation And Apoptosis

AbstractTreatment of bone cancer pain (BCP) caused by bone metastasis in advanced cancers remains a challenge in clinical oncology, and the underlying mechanisms of BCP are poorly understood. This study aimed to investigate the pathogenic roles of circular RNAs (circRNAs) in regulating cancer cell proliferation and BCP development. Eight differentially expressed circRNAs in the rat spinal cord were validated by agarose gel electrophoresis and Sanger sequencing. Expression of circRNAs and mRNAs was detected by quantitative RT-PCR. MTS assay and flow cytometry were performed to analyze cell proliferation and apoptosis, respectively. Differentially expressed mRNA profiles were characterized by deep RNA sequencing, hierarchical clustering, and functional categorization. The interactions among circRNAs, microRNAs (miRNAs), and mRNAs were predicted using TargetScan. Additionally, western blot was performed to determine the protein levels of Pax8, Isg15, and Cxcl10. Multiple circRNAs were differentially expressed in the spinal cords of BCP model rats; of these, circSlc7a11 showed the greatest increase in expression. The overexpression of circSlc7a11 significantly promoted cell proliferation and repressed apoptosis of LLC-WRC 256 and UMR-106 cells, whereas circSlc7a11 silencing produced the opposite effects. Altered expression of circSlc7a11 also induced substantial changes in the mRNA expression profiles of LLC-WRC 256 cells; these changes were linked to multiple apoptotic processes and signaling pathways, such as the chemokine signaling pathway, and formed a complex circRNA/miRNA/mRNA network. Additionally, Pax8, Isg15, and Cxc110 protein level in LLC-WRC 256 cells was consistent with the mRNA results. The circRNA circSlc7a11 regulates rat BCP development by modulating LLC-WRC 256 cell proliferation and apoptosis through multiple-signaling mechanisms.

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Uncontrolled Diabetes Mellitus Has No Major Influence on the Platelet Transcriptome

BioMed Research International ◽

10.1155/2018/8989252 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Thomas G. Nührenberg ◽

Marco Cederqvist ◽

Federico Marini ◽

Christian Stratz ◽

Björn A. Grüning ◽

...

Keyword(s):

Diabetes Mellitus ◽

Next Generation Sequencing ◽

Platelet Reactivity ◽

Platelet Rich Plasma ◽

Expression Profiles ◽

Bioinformatic Analysis ◽

Differentially Expressed ◽

Major Influence ◽

Next Generation ◽

Generation Sequencing

Background. Diabetes mellitus (DM) has been associated with increased platelet reactivity as well as increased levels of platelet RNAs in plasma. Here, we sought to evaluate whether the platelet transcriptome is altered in the presence of uncontrolled DM. Methods. Next-generation sequencing (NGS) was performed on platelet RNA for 5 patients with uncontrolled DM (HbA1c 9.0%) and 5 control patients (HbA1c 5.5%) with otherwise similar clinical characteristics. RNA was isolated from leucocyte-depleted platelet-rich plasma. Libraries of platelet RNAs were created separately for long RNAs after ribosomal depletion and for small RNAs from total RNA, followed by next-generation sequencing. Results. Platelets in both groups demonstrated RNA expression profiles characterized by absence of leukocyte-specific transcripts, high expression of well-known platelet transcripts, and in total 6,343 consistently detectable transcripts. Extensive statistical bioinformatic analysis yielded 12 genes with consistently differential expression at a lenient FDR < 0.1, thereof 8 protein-coding genes and 2 genes with known expression in platelets (MACF1 and ITGB3BP). Three of the four differentially expressed noncoding genes were YRNAs (RNY1, RNY3, and RNY4) which were all downregulated in DM. 23 miRNAs were differentially expressed between the two groups. Of the 13 miRNAs with decreased expression in the diabetic group, 8 belonged to the DLK1–DIO3 gene region on chromosome 14q32.2. Conclusions. In this study, uncontrolled DM had a remote impact on different components of the platelet transcriptome. Increased expression of MACF1, together with supporting predicted mRNA-miRNA interactions as well as reduced expression of RNYs in platelets, may reflect subclinical platelet activation in uncontrolled DM.

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Identification of differentially expressed circular RNAs in HeLa cells infected with Chlamydia trachomatis

Pathogens and Disease ◽

10.1093/femspd/ftz062 ◽

2019 ◽

Vol 77 (7) ◽

Author(s):

Yuanjun Liu ◽

Chunmin Hu ◽

Yina Sun ◽

Haoqing Wu ◽

Xiaojun Chen ◽

...

Keyword(s):

Chlamydia Trachomatis ◽

Signaling Pathways ◽

Hela Cells ◽

Expression Profiles ◽

Quantitative Polymerase Chain Reaction ◽

Host Cells ◽

Differentially Expressed ◽

Chlamydia Infection ◽

Circular Rnas ◽

Mrna Microarray

ABSTRACT Non-coding circular RNAs (circRNAs) have been shown to have important roles in many diseases; however, no study has indicated circRNAs are involved in Chlamydia trachomatis infection. In this study, we used circRNA microarray to measure the global circRNA expression profiles in HeLa cells with or without C. trachomatis serovar E (Ct.E) infection. CircRNA/miRNA/mRNA interactions were predicted and bioinformatics analyses were performed. The differentially expressed circRNAs were selected according to our criterion for validation by reverse-transcription and quantitative polymerase chain reaction (RT-qPCR). The mRNA microarray was used to detect the mRNA expression profiles after Ct.E infection. Among 853 differentially expressed circRNAs, 453 were upregulated and 400 were downregulated after Ct.E infection. Target miRNAs and miRNA-targeted mRNAs of these circRNAs were predicted. RT-qPCR analysis indicated hsa_circRNA_001226, hsa_circRNA_007046 and hsa_circRNA_400027 were elevated similar to those determined in the circRNA microarray analysis. The mRNA microarray results showed 915 genes were upregulated and 619 genes were downregulated after Ct.E infection. Thirty-four differentially expressed genes overlapped in the bioinformatics and mRNA microarray results. KEGG pathway analysis revealed several signaling pathways, including endocytosis, MAPK and PI3P-Akt signaling pathways, that were targeted by circRNAs may play important roles in Chlamydia infection. This study provides evidence that circRNAs in host cells are involved in the process of Chlamydia infection.

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Profiling and Bioinformatics Analysis of Differentially Expressed circRNAs in Spinal Ligament Tissues of Patients with Ankylosing Spondylitis

BioMed Research International ◽

10.1155/2020/7165893 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Jianqiang Kou ◽

Guoming Liu ◽

Xiangyun Liu ◽

Tianmi Li ◽

Ying Wei ◽

...

Keyword(s):

Ankylosing Spondylitis ◽

Bioinformatics Analysis ◽

Expression Profiles ◽

Potential Functions ◽

Serine Phosphorylation ◽

Differentially Expressed ◽

Circular Rnas ◽

Human Immune System ◽

Tissue Samples ◽

Spinal Ligament

Recent studies have reported that circular RNAs (circRNAs) play a crucial regulatory role in a variety of human diseases. However, the roles of circRNAs in ankylosing spondylitis (AS) remain unclear. In this study, we conducted circRNA expression profiling of the spinal ligament tissues of patients with AS by RNA sequencing (RNA-seq) and analyzed the potential functions of differentially expressed circRNA by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to investigate the potential mechanisms associated with AS. The results showed that a total of 1,172 circRNAs were detected in the spinal ligament tissue samples, of which 123 circRNAs were significantly differentially expressed by a fold change≥1.5 and p value < 0.05. Among these, 57 circRNAs were upregulated, and 66 were downregulated. GO and KEGG analyses demonstrated that the differentially expressed circRNAs were mainly involved in the regulation of biological processes of peptidyl-serine phosphorylation and human immune system that may be related to AS. In addition, the circRNA/miRNA interaction networks were established to predict the potential roles of differentially expressed circRNAs by bioinformatics analysis. Taken together, these results revealed the expression profiles of circRNAs and the potential functions of the differentially expressed circRNAs in the spinal ligament tissue of patients with AS, which may provide new clues for understanding the mechanisms associated with AS, and proceed to identify novel potential molecular targets for the diagnoses and treatment of AS.

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Profiling and bioinformatics analysis of differentially expressed circular RNAs in human intervertebral disc degeneration

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmz036 ◽

2019 ◽

Vol 51 (6) ◽

pp. 571-579 ◽

Cited By ~ 7

Author(s):

Shunmin Wang ◽

Jingchuan Sun ◽

Haisong Yang ◽

Weiguo Zou ◽

Bing Zheng ◽

...

Keyword(s):

Intervertebral Disc ◽

Disc Degeneration ◽

Intervertebral Disc Degeneration ◽

Expression Profiles ◽

Differentially Expressed ◽

Circular Rnas ◽

Functional Changes ◽

Qrt Pcr ◽

Reverse Transcription Pcr ◽

Microarray Expression

AbstractThe functional changes of nucleus pulposus (NP) cells are considered to be the initiating factors of intervertebral disc degeneration (IDD), and the differentially expressed circRNAs in NP cells may play an important role in the process of IDD. To identify circular RNAs (circRNAs) associated with human IDD, we isolated the NP cells from human degenerated and non-degenerated intervertebral disc and identified NP cells by microscopy and cell proliferation. CircRNA microarray expression profiles were obtained from NP cells of degenerated and non-degenerated intervertebral disc and further validated by quantitative reverse transcription PCR (qRT-PCR). The expression data were analyzed by bioinformatics. Microarray analysis identified 7294 circRNAs differentially expressed in degenerated human IDD NP cells. Among them, 3724 circRNAs were up-regulated and 3570 circRNAs were down-regulated by more than 2 folds. After validating by qRT-PCR, we predicted the possible miRNAs of the top dysregulated circRNAs using TargetScan, and miRanda. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the most modulated circRNAs regulate the viability, degradation, apoptosis and oxidative stress in NP cells, and the possible mechanism underlying IDD was discussed. These results revealed that circRNAs may play a role in IDD and might be a promising candidate molecular target for gene therapy.

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Microarray Expression Profile of Circular RNAs in Plasma from Primary Biliary Cholangitis Patients

Cellular Physiology and Biochemistry ◽

10.1159/000485487 ◽

2017 ◽

Vol 44 (4) ◽

pp. 1271-1281 ◽

Cited By ~ 8

Author(s):

Jiajia Zheng ◽

Zhenrong Li ◽

Tiancheng Wang ◽

Yang Zhao ◽

Yongfeng Wang

Keyword(s):

Expression Profile ◽

Expression Profiles ◽

Characteristic Curve ◽

Group Versus ◽

Target Prediction ◽

Differentially Expressed ◽

Circular Rnas ◽

Primary Biliary Cholangitis ◽

Healthy Controls ◽

Qrt Pcr

Background/Aims: Circular RNAs (circRNAs) play a crucial role in the occurrence of several diseases, including autoimmune diseases. However, their role in primary biliary cholangitis (PBC) remains unclear. Here, we aimed to determine the circRNA expression profile in plasma from PBC patients and further explore the value of circRNA in diagnosing PBC. Methods: CircRNA microarrays were used to determine circRNA expression profiles in plasma samples from 6 PBC patients and 6 healthy controls. Statistical analyses identified differentially expressed circRNAs, and these circRNAs were verified by qRT-PCR in 29 PBC patients and 30 healthy controls. MicroRNA (miRNA) target prediction software identified putative miRNA response elements (MREs), which were used to construct a map of circRNA-miRNA interactions for the differentially expressed circRNAs. Results: Our results indicated that there were 18 up-regulated and 4 down-regulated circular RNAs in the plasma from PBC patients compared with that from healthy individuals. Among the differentially expressed circRNAs, hsa_circ_402458 (P=0.0033), hsa_circ_087631 and hsa_circ_406329 (P=0.0185) were up-regulated, and hsa_circ_407176 (P=0.0066) and hsa_circ_082319 were down-regulated in the PBC group versus the healthy group as demonstrated by qRT-PCR. In particular, hsa_circ_402458 was significantly higher in PBC patients not receiving UDCA treatment than in PBC patients receiving UDCA treatment (P=0.0338). The area under the receiver operating characteristic curve for hsa_circ_402458 for diagnosing PBC was 0.710 (P=0.005). For hsa_circ_402458, two putative miRNA targets, hsa-miR-522-3p and hsa-miR-943, were predicted. Conclusions: circRNA dysregulation may play a role in PBC pathogenesis, and hsa_circ_402458 shows promise as a candidate biomarker for PBC.

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Screening and functional prediction of differentially expressed circular RNAs in human glioma of different grades

Aging ◽

10.18632/aging.202192 ◽

2020 ◽

Author(s):

Xiuchao Geng ◽

Yuhao Zhang ◽

Qiang Li ◽

Wang Xi ◽

Wentao Yu ◽

...

Keyword(s):

Differentially Expressed ◽

Circular Rnas ◽

Human Glioma ◽

Functional Prediction

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