scholarly journals Microarray Expression Profile and Functional Analysis of Circular RNAs in Osteosarcoma

2017 ◽  
Vol 43 (3) ◽  
pp. 969-985 ◽  
Author(s):  
Weihai Liu ◽  
Jiajun Zhang ◽  
Changye Zou ◽  
Xianbiao Xie ◽  
Yongqian Wang ◽  
...  

Background/Aims: Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. However, the molecular mechanisms regulating osteosarcoma tumorigenesis and progression are still poorly understood. Circular RNAs (circRNAs) have been identified as microRNA sponges and are involved in many important biological processes. This study aims to investigate the global changes in the expression pattern of circRNAs in osteosarcoma and provide a comprehensive understanding of differentially expressed circRNAs. Methods: Microarray based circRNA expression was determined in osteosarcoma cell lines and compared with hFOB1.19, which was used as the normal control. We confirmed the microarray data by real time-qPCR in both osteosarcoma cell lines and tissues. The circRNA/microRNA/mRNA interaction network was predicted using bioinformatics. Gene Ontology analysis and 4 annotation tools for pathway analysis (KEGG, Biocarta, PANTHER and Reactome) were used to predict the functions of differentially expressed circRNAs. Results: We revealed a number of differentially expressed circRNAs and 12 of them were confirmed, which suggests a potential role of circRNAs in OS. Among these differentially expressed circRNAs, hsa_circRNA_103801 was up-regulated in both osteosarcoma cell lines and tissues, while hsa_circRNA_104980 was down-regulated. The most likely potential target miRNAs for hsa_circRNA_103801 include hsa-miR-370-3p, hsa-miR-338-3p and hsa-miR-877-3p, while the most potential target miRNAs of hsa_circRNA_104980 consist of hsa-miR-1298-3p and hsa-miR-660-3p. Functional analysis found that hsa_circRNA_103801 was involved in pathways in cancer, such as the HIF-1, VEGF and angiogenesis pathway, the Rap1 signaling pathway and the PI3K-Akt signaling pathway, while hsa_circRNA_104980 was related to some pathways such as the tight junction pathway. Conclusions: This study has identified the comprehensive expression profile of circRNAs in osteosarcoma for the first time. And the ceRNA network prediction and bioinformatics functional analysis could provide a comprehensive understanding of hsa_circRNA_103801 and hsa_circRNA_104980, which may be involved in the initiation and progression of osteosarcoma. The present study indicates that circRNAs may play important roles in osteosarcoma and thus serve as biomarkers of osteosarcoma diagnosis and treatment.

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11420
Author(s):  
Haijin Zhang ◽  
Xue Song ◽  
Zongyan Teng ◽  
Sujun Cheng ◽  
Weigang Yu ◽  
...  

Background Osteoporosis (OP) is a systemic disease with bone loss and microstructural deterioration. Numerous noncoding RNAs (ncRNAs) have been proved to participate in various diseases, especially circular RNAs (circRNAs). However, the expression profile and mechanisms underlying circRNAs in male osteoporosis have not yet been explored. Methods The whole transcriptome expression profile and differences in mRNAs, circRNAs, and microRNAs (miRNAs) were investigated in peripheral blood samples of patients with osteoporosis and healthy controls consisting of males ≥ 60-years-old. Results A total of 398 circRNAs, 51 miRNAs, and 642 mRNAs were significantly and differentially expressed in osteoporosis compared to healthy controls. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the host genes of significantly differentially expressed circRNAs were mainly enriched in the regulation of cell cycle process: biological process (BP), organelle part cellular components (CC), protein binding molecular function (MF), Toll-like receptor signaling pathway, tumor necrosis factor (TNF) signaling pathway, and thyroid hormone signaling pathway. circRNA-miRNA-mRNA regulatory network was constructed using the differentially expressed RNAs. Moreover, key circRNAs (hsa_circ_0042409) in osteoporosis were discovered and validated by qPCR. Conclusions The key cicrRNAs plays a major role in the pathogenesis of osteoporosis and could be used as potential biomarkers or targets in the diagnosis and treatment of osteoporosis.


Author(s):  
Pan Ge ◽  
Jian Zhang ◽  
Liang Zhou ◽  
Mo-qi Lv ◽  
Yi-xin Li ◽  
...  

Abstract Background Non-obstructive azoospermia (NOA) is a multifactorial disorder whose molecular basis remains largely unknown. Circular RNAs (CircRNAs), a novel class of endogenous RNAs, have been recognized to play important roles in many biological processes. However, little is known about the expression patterns and functions of circRNAs in human testes involved in NOA. Methods In this study, the testicular circRNA expression profile were explored in NOA patients and the controls by high-throughput circRNA microarray. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to confirm the microarray data. Bioinformatics analyses including the circRNA/miRNA/mRNA interaction network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to predict the functions of differentially expressed circRNAs. Results A total of 368 differentially down-regulated and 526 up-regulated circRNAs were detected in NOA patients. These findings have been verified by qRT-PCR on 6 selected circRNAs. Among these differentially expressed circRNAs, the hsa_circRNA_0023313 was obviously up-regulated in testicular tissue of NOA patients. The most likely potential target miRNA for hsa_circRNA_0023313 include hsa-miR-520d-3p, hsa-miR-373-3p, hsa-miR-372-3p, hsa-miR-302c-3p and hsa-miR-130b-5p. Function analysis indicated that hsa_circRNA_0023313 was ubiquitin-protein transferase activity and chromatin binding. KEGG analysis revealed that the top five pathways related to hsa_circRNA_0023313 were endocytosis, meiosis, FoxO signaling pathway, ubiquitin mediated proteolysis and AMPK signaling pathway. Conclusions This is the first report that the testicular circRNA expression profile is altered in NOA patients indicating circRNAs might play important roles in regulating spermatogenesis and be potential biomarkers for the diagnosis and treatment of NOA.


2018 ◽  
Vol 50 (1) ◽  
pp. 342-352 ◽  
Author(s):  
Yue Fan ◽  
Xin Xia ◽  
Yingying Zhu ◽  
Wenwen Diao ◽  
Xiaoli Zhu ◽  
...  

Background/Aims: A growing body of evidence has suggested that circular RNAs (circRNAs) have crucial functions in the regulation of gene expression, and their dysregulation has been implicated in various types of cancers. However, the roles of circRNAs in laryngeal cancer remain largely unknown. This study investigated the global changes in the expression pattern of circRNAs in laryngeal squamous cell carcinoma (LSCC) to identify potential differentially expressed circRNAs. Methods: Microarray-based circRNA expression was determined in LSCC and paired normal laryngeal tissues. Pathway analyses of the genes producing differentially expressed circRNAs were performed to predict the function of circRNAs using standard enrichment computational methods. Expression levels of candidate circRNAs and microRNAs (miRNAs) were detected by quantitative real-time PCR. The circRNA/ miRNA interactions were constructed using bioinformatics methods to predict the binding of miRNA with circRNA. Results: We identified 506 differentially expressed circRNAs from human LSCC and normal laryngeal mucosa tissues. We confirmed that hsa_circ_0044520 and hsa_circ_0044529 were significantly upregulated in LSCC tissues. The most likely potential target miRNAs for hsa_ circ_0044520 and hsa_circ_0044529 were hsa-miR-4726-5p and hsa-miR-4640-5p, respectively. Functional analysis showed that hsa_circ_0044520 and hsa_circ_0044529 were involved in the process of collagen synthesis. Conclusion: Competitive endogenous RNA network prediction and bioinformatics functional analysis revealed that hsa_circ_0044520 and hsa_circ_0044529 play important regulatory roles by sponging hsa-miR-4726-5p and hsa-miR-4640-5p, thereby providing novel insights into the tumorigenesis of LSCC.


Author(s):  
Xuehui Wang ◽  
Changle Ji ◽  
Jiashu Hu ◽  
Xiaochong Deng ◽  
Wenfang Zheng ◽  
...  

Abstract Background Circular RNAs (circRNAs), a novel class of endogenous RNAs, have shown to participate in the development of breast cancer (BC). Hsa_circ_0005273 is a circRNA generated from several exons of PTK2. However, the potential functional role of hsa_circ_0005273 in BC remains largely unknown. Here we aim to evaluate the role of hsa_circ_0005273 in BC. Methods The expression level of hsa_circ_0005273 and miR-200a-3p were examined by RT-qPCR in BC tissues and cell lines. The effect of knocking down hsa_circ_0005273 in BC cell lines were evaluated by examinations of cell proliferation, migration and cell cycle. In addition, xenografts experiment in nude mice were performed to evaluate the effect of hsa_circ_0005273 in BC. RNA immunoprecipitation assay, RNA probe pull-down assay, luciferase reporter assay and fluorescence in situ hybridization were conducted to confirm the relationship between hsa_circ_0005273, miR-200a-3p and YAP1. Results Hsa_circ_0005273 is over-expressed in BC tissues and cell lines, whereas miR-200a-3p expression is repressed. Depletion of hsa_circ_0005273 inhibited the progression of BC cells in vitro and in vivo, while overexpression of hsa_circ_0005273 exhibited the opposite effect. Importantly, hsa_circ_0005273 upregulated YAP1 expression and inactivated Hippo pathway via sponging miR-200a-3p to promote BC progression. Conclusions Hsa_circ_0005273 regulates the miR-200a-3p/YAP1 axis and inactivates Hippo signaling pathway to promote BC progression, which may become a potential biomarker and therapeutic target.


Animals ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 849
Author(s):  
Yu Liu ◽  
Liping Li ◽  
Zhiping Luo ◽  
Rui Wang ◽  
Ting Huang ◽  
...  

Our previous study showed that human-derived Streptococcus agalactiae (serotype V) could infect tilapia, but the mechanism underlying the cross-species infection remains unrecognized. In this study, a multi-omics analysis was performed on human-derived S.agalactiae strain NNA048 (virulent to tilapia, serotype V, ST1) and human-derived S.agalactiae strain NNA038 (non-virulent to tilapia, serotype V, ST1). The results showed that 907 genes (504 up/403 down) and 89 proteins (51 up/38 down) were differentially expressed (p < 0.05) between NNA038 and NNA048. Among them, 56 genes (proteins) were altered with similar trends at both mRNA and protein levels. Functional annotation of them showed that the main differences were enriched in the arginine deiminase system signaling pathway and biotin metabolism signaling pathway: gdhA, glnA, ASL, ADI, OTC, arcC, FabF, FabG, FabZ, BioB and BirA genes may have been important factors leading to the pathogenicity differences between NNA038 and NNA048. We aimed to provide a comprehensive analysis of the human-derived serotype V ST1 S.agalactiae strains, which were virulent and non-virulent to tilapia, and provide a more comprehensive understanding of the virulence mechanism.


2017 ◽  
Vol 44 (4) ◽  
pp. 1271-1281 ◽  
Author(s):  
Jiajia Zheng ◽  
Zhenrong Li ◽  
Tiancheng Wang ◽  
Yang Zhao ◽  
Yongfeng Wang

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.


2021 ◽  
Vol 11 ◽  
Author(s):  
Ji Wang ◽  
Zhongxiu Yang ◽  
Canming Chen ◽  
Yang Xu ◽  
Hongguang Wang ◽  
...  

Autism is a common disease that seriously affects the quality of life. The role of circular RNAs (circRNAs) in autism remains largely unexplored. We aimed to detect the circRNA expression profile and construct a circRNA-based competing endogenous RNA (ceRNA) network in autism. Valproate acid was used to establish an in vivo model of autism in mice. A total of 1,059 differentially expressed circRNAs (477 upregulated and 582 downregulated) in autism group was identified by RNA sequencing. The expression of novel_circ_015779 and novel_circ_035247 were detected by real-time PCR. A ceRNA network based on altered circRNAs was established, with 9,715 nodes and 150,408 edges. Module analysis was conducted followed by GO and KEGG pathway enrichment analysis. The top three modules were all correlated with autism-related pathways involving “TGF-beta signaling pathway,” “Notch signaling pathway,” “MAPK signaling pathway,” “long term depression,” “thyroid hormone signaling pathway,” etc. The present study reveals a novel circRNA involved mechanisms in the pathogenesis of autism.


2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Lin Wei ◽  
Xia Li ◽  
Lijuan Wang ◽  
Yanyan Song ◽  
Hongmei Dong

Hypoxic ischemic encephalopathy (HIE) is classified as a sort of serious nervous system syndrome that occurs in the early life period. Noncoding RNAs had been confirmed to have crucial roles in human diseases. So far, there were few systematical and comprehensive studies towards the expression profile of RNAs in the brain after hypoxia ischemia. In this study, 31 differentially expressed microRNAs (miRNAs) with upregulation were identified. In addition, 5512 differentially expressed mRNAs, long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) were identified in HIE groups. Bioinformatics analysis showed these circRNAs and mRNAs were significantly enriched in regulation of leukocyte activation, response to virus, and neutrophil degranulation. Pathway and its related gene network analysis indicated that HLA − DPA1, HLA − DQA2, HLA − DQB1, and HLA − DRB4 have a more crucial role in HIE. Finally, miRNA-circRNA-mRNA interaction network analysis was also performed to identify hub miRNAs and circRNAs. We found that miR-592 potentially targeting 5 circRNAs, thus affecting 15 mRNA expressions in HIR. hsa_circ_0068397 and hsa_circ_0045698 were identified as hub circRNAs in HIE. Collectively, using RNA-seq, bioinformatics analysis, and circRNA/miRNA interaction prediction, we systematically investigated the differentially expressed RNAs in HIE, which could give a new hint of understanding the pathogenesis of HIE.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Chao Bai ◽  
Wenwen Yang ◽  
Yao Lu ◽  
Wei Wei ◽  
Zongbao Li ◽  
...  

This study is to identify the circular RNA (circRNA) expression profile that is functionally related to pancreatic islet β-cell autophagy and their potential regulation mechanisms in type 2 diabetes mellitus (T2DM). T2DM rat model was constructed by administration of high-fat and high-sugar diet. β-cells were isolated from islets by flow cytometry. CircRNA expression profile in β-cells was detected by circRNA microarrays, and the differentially expressed circRNAs were identified and validated by qRT-PCR. MicroRNA (miRNA) target prediction software and multiple bioinformatic approaches were used to construct a map of circRNA-miRNA interactions for the differentially expressed circRNAs. A total of 825 differentially expressed circular transcripts were identified in T2DM rats compared with control rats, among which 388 were upregulated and 437 were downregulated. Ten circRNAs were identified to have significant differences by qRT-PCR. GO analysis enriched terms such as organelle membrane and protein binding and the top enriched pathways for the circRNAs included MAPK signaling pathway. The differentially expressed circRNAs might involve in MAPK signaling pathway, apoptosis, and Ras signaling pathway. We speculate that these circRNAs, especially rno_circRNA_008565, can regulate the autophagy of islet β-cells via interactions with miRNA. Dysregulation of several circRNAs may play a role in T2DM development, and rno_circRNA_008565 may be a potential regulator of β-cell autophagy.


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