scholarly journals CircRNA hsa_circ_0008500 Acts as a miR-1301-3p Sponge to Promote Osteoblast Mineralization by Upregulating PADI4

2020 ◽  
Vol 8 ◽  
Author(s):  
Qiaoli Zhai ◽  
Yi Zhao ◽  
Linping Wang ◽  
Yan Dai ◽  
Peiqing Zhao ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Suppressive Effect ◽  
Arginine Deiminase ◽  
Circular Rnas ◽  
Matrix Mineralization ◽  
Elevated Expression ◽  
Ubiquitin Proteasome ◽  
Mineralization Processes ◽  
Critical Binding

Circular RNAs (circRNAs) are regarded as pivotal regulators in bone metabolism. However, the role of circRNAs in osteoblast mineralization remains largely unknown. Herein, we explored the expression profiles of circRNAs in 4 groups of osteoblasts with varying mineralization processes. Hsa_circ_0008500 (circ8500), which is upregulated in the RNA-seq data, is sifted through 194 candidate circRNAs in osteoblasts during mineralization. We characterize the features of novel circRNAs and find that the elevated expression of circ8500 promotes osteoblast mineralization. Mechanistically, circ8500 contains a critical binding site for miR-1301-3p. We further show that circ8500 competitively binds miR-1301-3p to abolish its suppressive effect on peptidyl arginine deiminase 4 (PADI4). PADI4 works as a binding partner of RUNX2 and stabilizes its protein expression levels by inhibiting the ubiquitin-proteasome pathway. This work provides new insights on the circRNA patterns in osteoblasts and the role of PADI4 in matrix mineralization.

scholarly journals Ubiquitin-Specific Protease 8 Mutant Corticotrope Adenomas Present Unique Secretory and Molecular Features and Shed Light on the Role of Ubiquitylation on ACTH Processing

2019 ◽  
Vol 110 (1-2) ◽  
pp. 119-129 ◽  
Author(s):  
Antonella Sesta ◽  
Maria Francesca Cassarino ◽  
Mariarosa Terreni ◽  
Alberto G. Ambrogio ◽  
Laura Libera ◽  
...  
Keyword(s):  
Protein Degradation ◽  
Pituitary Adenomas ◽  
Expression Profiles ◽  
Primary Cultures ◽  
Acth Secretion ◽  
Specific Protease ◽  
Ubiquitin Proteasome ◽  
Ubiquitin Specific Protease ◽  
Acth Secreting

Background: Somatic mutations in the ubiquitin-specific protease 8 (USP8) gene have recently been shown to occur in ACTH-secreting pituitary adenomas, thus calling attention to the ubiquitin system in corticotrope adenomas. Objectives: Assess the consequences of USP8 mutations and establish the role of ubiquitin on ACTH turnover in human ACTH-secreting pituitary adenomas. Methods: USP8 mutation status was established in 126 ACTH-secreting adenomas. Differences in ACTH secretion and POMC expression from adenoma primary cultures and in microarray gene expression profiles from archival specimens were sought according to USP8 sequence. Ubiquitin/ACTH coimmunoprecipitation and incubation with MG132, a proteasome inhibitor, were performed in order to establish whether ubiquitin plays a role in POMC/ACTH degradation in corticotrope adenomas. Results: USP8 mutations were identified in 29 adenomas (23%). Adenomas presenting USP8 mutations secreted greater amounts of ACTH and expressed POMC at higher levels compared to USP wild-type specimens. USP8 mutant adenomas were also more sensitive to modulation by CRH and dexamethasone in vitro. At microarray analysis, genes associated with endosomal protein degradation and membrane components were downregulated in USP8 mutant adenomas as were AVPR1B, IL11RA, and PITX2. Inhibition of the ubiquitin-proteasome pathway increased ACTH secretion and POMC itself proved a target of ubiquitylation, independently of USP8 sequence status. Conclusions: Our study has shown that USP8 mutant ACTH-secreting adenomas present a more “typical” corticotrope phenotype and reduced expression of several genes associated with protein degradation. Further, ubiquitylation is directly involved in intracellular ACTH turnover, suggesting that the ubiquitin-proteasome system may represent a target for treatment of human ACTH-secreting adenomas.

Identification and Characterization of Rice Circular RNAs Responding to Xanthomonas Oryzae pv. Oryzae Invasion

2021 ◽  
Author(s):  
Peihong Wang ◽  
Sai Wang ◽  
Yan Wu ◽  
Wenhan Nie ◽  
Ayizekeranmu Yiming ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Circular Rnas ◽  
Pathogen Invasion ◽  
Rice Leaves ◽  
Transcriptional Gene Regulation ◽  
Identification And Characterization ◽  
Host Genes

Abstract BackgroundThe emerging role of circular RNAs (circRNAs) in various biological processes have advanced our knowledge of transcriptional and post-transcriptional gene regulation. The number and expression of plant circRNAs vary with species and treatments. However, the expression profile and the potential role of circRNAs during plant response to pathogen invasion are still elusive. ResultsIn this study, we identified 3517 circRNAs from PXO99A-infected rice leaves using the ribosomal RNA (rRNA) depleted RNA-Sequencing technique coupled with the CIRI2 and CIRCexplorer2 pipeline. Among them, 2994 (85.13%) circRNAs arised from the exons of their parent genes, 1214 circRNAs were previously unknown and 276 circRNAs exhibited differential expression profiles upon PXO99A infection over time. In addition, 31 differentially expressed circRNAs (DEcircRNAs) were predicted as the corresponding 121 miRNAs sponges. Functional analysis of both host genes and target mRNAs suggested that these identified circRNAs might play an important role in reprogramming rice responses to PXO99A invasion, mainly by mediating photorespiration, chloroplast, peroxisome and diterpenoid biosynthesis associated pathways.ConclusionThese results inferred a potential functional role of circRNAs in the regulation of rice immunity and provide novel clues for revealing the molecular mechanisms of rice-PXO99A interaction.

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

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.

scholarly journals Construction and investigation of a circRNA-associated ceRNA regulatory network in Tetralogy of Fallot

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Haifei Yu ◽  
Xinrui Wang ◽  
Hua Cao
Keyword(s):  
Tetralogy Of Fallot ◽  
Heart Development ◽  
Expression Profiles ◽  
Screening Strategy ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Tissue Samples ◽  
Cerna Network ◽  
Positive Correlations

Abstract Background As the most frequent type of cyanotic congenital heart disease (CHD), tetralogy of Fallot (TOF) has a relatively poor prognosis without corrective surgery. Circular RNAs (circRNAs) represent a novel class of endogenous noncoding RNAs that regulate target gene expression posttranscriptionally in heart development. Here, we investigated the potential role of the ceRNA network in the pathogenesis of TOF. Methods To identify circRNA expression profiles in TOF, microarrays were used to screen the differentially expressed circRNAs between 3 TOF and 3 control human myocardial tissue samples. Then, a dysregulated circRNA-associated ceRNA network was constructed using the established multistep screening strategy. Results In summary, a total of 276 differentially expressed circRNAs were identified, including 214 upregulated and 62 downregulated circRNAs in TOF samples. By constructing the circRNA-associated ceRNA network based on bioinformatics data, a total of 19 circRNAs, 9 miRNAs, and 34 mRNAs were further screened. Moreover, by enlarging the sample size, the qPCR results validated the positive correlations between hsa_circ_0007798 and HIF1A. Conclusions The findings in this study provide a comprehensive understanding of the ceRNA network involved in TOF biology, such as the hsa_circ_0007798/miR-199b-5p/HIF1A signalling axis, and may offer candidate diagnostic biomarkers or potential therapeutic targets for TOF. In addition, we propose that the ceRNA network regulates TOF progression.

scholarly journals Circular RNA EPB41 Expression Predicts Unfavorable Prognoses in NSCLC by Regulating miR-486-3p/eIF5A Axis-Mediated Stemness

2021 ◽  
Author(s):  
Xiyu Liu ◽  
Yue Wu ◽  
Yuqing Lou ◽  
Mingming Jin ◽  
Xue Li ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Sequencing ◽  
Expression Profiles ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Reporter System ◽  
Bioinformatics Analyses

Abstract Dysregulation of circular RNAs (circRNAs) has recently been found to play an important role in the progression and development of cancers such as non-small cell lung cancer (NSCLC). Yet the functions of many circRNAs in NSCLC remain unclear. In this study, the circRNA expression profiles in NSCLC tumor tissues and adjacent non-tumorous tissues were detected by high-throughput sequencing. Bioinformatics analyses, the dual-luciferase reporter system, fluorescence in situ hybridization (FISH) and miRNA/mRNA high-throughput sequencing were used to identify circ-EPB41 and its downstream target. The subcutaneous tumor/caudal vein transfer mouse model was used for tumor growth and invasion analysis. The results show that the circ-EPB41 was upregulated in NSCLC tissues and cell lines. Increased circ-EPB41 expression in NSCLC was significantly correlated with malignant characteristics, and positive to post-surgical overall survival of NSCLC patients. Reduced circ-EPB41 expression in NSCLC decreased cell proliferation and invasion in both in vitro and in vivo experiments. The miRNA/mRNA high-throughput sequencing suggested that downregulation of circ-EPB41 promoted microRNA (miR)-486-3p and suppressed eukaryotic translation initiation factor 5A (eIF5A) expression. Luciferase reporter experiments confirmed that miR-486-3p/eIF5A were downstream targets of circ-EPB41. In addition, we also found that downregulation of circ-EPB41 suppressed self-renewal and decreased expression of stemness markers SOX2, OCT-4, Nanog and CD133 by sponging miR-486-3p to enhance eIF5A expression. Taken togeter, these data revealed the important role of circ-EPB41 in regulating NSCLC cell invasion and proliferation by modifying miR-486-3p/eIF5A axis-mediated stemness. We believe our study provides a novel perspective regarding the role of circRNAs in NSCLC progression.

scholarly journals Exosomal microRNAs and other non-coding RNAs as colorectal cancer biomarkers: a review

Mutagenesis ◽  
2019 ◽  
Vol 35 (3) ◽  
pp. 243-260 ◽  
Author(s):  
Antonio Francavilla ◽  
Szimonetta Turoczi ◽  
Sonia Tarallo ◽  
Pavel Vodicka ◽  
Barbara Pardini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Expression Profiles ◽  
Predictive Markers ◽  
Circular Rnas ◽  
Rna Molecules ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Prognostic And Predictive Markers

Abstract The circulating human transcriptome, which includes both coding and non-coding RNA (ncRNA) molecules, represents a rich source of potential biomarkers for colorectal cancer (CRC) that has only recently been explored. In particular, the release of RNA-containing extracellular vesicles (EVs), in a multitude of different in vitro cell systems and in a variety of body fluids, has attracted wide interest. The role of RNA species in EVs is still not fully understood, but their capacity to act as a form of distant communication between cells and their higher abundance in association with cancer demonstrated their relevance. In this review, we report the evidence from both in vitro and human studies on microRNAs (miRNAs) and other ncRNA profiles analysed in EVs in relation to CRC as diagnostic, prognostic and predictive markers. The studies so far highlighted that, in exosomes, the most studied category of EVs, several miRNAs are able to accurately discriminate CRC cases from controls as well as to describe the progression of the disease and its prognosis. Most of the time, the in vitro findings support the miRNA profiles detected in human exosomes. The expression profiles measured in exosomes and other EVs differ and, interestingly, there is a variability of expression also among different subsets of exosomes according to their proteic profile. On the other hand, evidence is still limited for what concerns exosome miRNAs as early diagnostic and predictive markers of treatment. Several other ncRNAs that are carried by exosomes, mostly long ncRNAs and circular RNAs, seem also to be dysregulated in CRC. Besides various technical challenges, such as the standardisation of EVs isolation methods and the optimisation of methodologies to characterise the whole spectrum of RNA molecules in exosomes, further studies are needed in order to elucidate their relevance as CRC markers.

scholarly journals Circular RNAs as Competing Endogenous RNAs in Cardiovascular and Cerebrovascular Diseases: Molecular Mechanisms and Clinical Implications

2021 ◽  
Vol 8 ◽  
Author(s):  
Xue Min ◽  
Dong-liang Liu ◽  
Xing-dong Xiong
Keyword(s):  
Molecular Mechanism ◽  
Molecular Mechanisms ◽  
Suppressive Effect ◽  
Cerebrovascular Diseases ◽  
Circular Rnas ◽  
Clinical Implications ◽  
Future Directions ◽  
Rna Molecules ◽  
Competing Endogenous Rnas

Circular RNAs (circRNAs) represent a novel class of widespread and diverse endogenous RNA molecules. This unusual class of RNA species is generated by a back-splicing event of exons or introns, resulting in a covalently closed circRNA molecule. Accumulating evidence indicates that circRNA plays an important role in the biological functions of a network of competing endogenous RNA (ceRNA). CircRNAs can competitively bind to miRNAs and abolish the suppressive effect of miRNAs on target RNAs, thus regulating gene expression at the posttranscriptional level. The role of circRNAs as ceRNAs in the pathogenesis of cardiovascular and cerebrovascular diseases (CVDs) has been recently reported and highlighted. Understanding the underlying molecular mechanism could aid the discovery of therapeutic targets or strategies against CVDs. Here, we review the progress in studying the role of circRNAs as ceRNAs in CVDs, with emphasis on the molecular mechanism, and discuss future directions and possible clinical implications.

scholarly journals Role of Circular RNAs in Preeclampsia

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Ningyi Jia ◽  
Jian Li
Keyword(s):  
Expression Profiles ◽  
Noncoding Rnas ◽  
Mechanisms Of Action ◽  
Circular Rnas ◽  
Hypertensive Disorder ◽  
Mortality And Morbidity ◽  
Profound Impact ◽  
Current State ◽  
Hypertensive Disorder Of Pregnancy

Circular RNAs (circRNAs) are noncoding RNAs characterized by circular covalently closed structures, which are generated by back-splicing. circRNA is more stable and conserved than linear RNA and exists in various organisms. Preeclampsia (PE), a common hypertensive disorder of pregnancy, has a profound impact on maternal and neonatal mortality and morbidity. Recent studies demonstrated that circRNAs were differentially expressed in PE maternal-fetal interface compared with those in the control and might mediate pathological processes in pregnancy complications. However, the mechanisms of action of circRNAs in PE are still unclear. Here, we provide a comprehensive review on the current state of knowledge on circRNAs associated with PE. We summarize the known expression profiles of circRNAs and discuss their potential application as biomarkers of PE. The possible mechanisms underlying circRNA dysregulation in the etiology of PE are also explored.

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

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.

scholarly journals The role of circular RNA circ_0008285 in gestational diabetes mellitus by regulating the biological functions of trophoblasts

2021 ◽  
Vol 54 (1) ◽  
Author(s):  
Haitian Chen ◽  
Shaofeng Zhang ◽  
Yanxin Wu ◽  
Zhuyu Li ◽  
Dongyu Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
High Throughput Sequencing ◽  
Expression Profiles ◽  
Circular Rna ◽  
Circular Rnas ◽  
Invasion And Migration ◽  
And Migration

Abstract Background Circular RNAs (circRNAs) has emerged as vital regulator involved in various diseases. In this study, we identified and investigated the potential circRNAs involved in gestational diabetes mellitus (GDM). Methods High-throughput sequencing was used to collect the plasma circRNAs expression profiles of GDM patients. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) was used to measure the expressions of circ_0008285 and circ_0001173 in the plasma specimens. The Pearson’s correlation test was employed to assess the correlation between 2 circRNAs expression and the clinicopathologic data. Two circRNAs expression was verified in high glucose (HG)-induced HTR-8/SVneo cells. MTS, transwell assay was used to evaluate the effects of circ_0008285 expression on HG-induced HTR-8/SVneo cells. The network of circ_0008285 was constructed using cytocape. Results In GDM patients, the expression of circ_0008285 was significantly upregulated, while that of circ_0001173 was decreased. Circ_0008285 was significantly correlated with the total cholesterol and LDL-C levels. Circ_0001173 was significantly correlated with glycated hemoglobin. HG promoted the proliferation, invasion, and migration in HTR-8/SVneo cells, while the knockdown of circ_0008285 exerted reverse effects. In addition, network construction exhibited that circ_0008285 had 45 miRNA binding sites, which correlated with 444 mRNA. Conclusions circ_0008285 plays an important role and provides a clue for the usage of therapeutic targets in the development of GDM.

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