A Comprehensive Analysis of the circRNA–miRNA–mRNA Network in Osteocyte-Like Cell Associated with Mycobacterium Leprae Infection

Abstract Bone formation and loss are the characteristic clinical manifestations of leprosy, but the mechanisms underlying the bone remodeling with Mycobacterium leprae (M. leprae) infection are unclear. Osteocytes may have a role through regulating the differentiation of osteogenic lineages. To investigate osteocyte-related mechanisms in leprosy, we treated osteocyte-like cell with N-glycosylated muramyl dipeptide (N.g MDP). RNA-seq analysis showed 724 differentially expressed messenger RNAs (mRNAs) and 724 differentially expressed circular RNA (circRNAs). Of these, we filtered through eight osteogenic-related differentially expressed genes, according to the characteristic of competing endogenous RNA, PubMed databases, and bioinformation analysis, including TargetScan, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes. Based on these results, we built a circRNA–microRNA (miRNA)–mRNA triple network. Quantitative reverse-transcription polymerase chain reaction and western blots analyses confirmed decreased Clock expression in osteocyte-like cell, while increased in bone mesenchymal stem cells (BMSCs), implicating a crucial factor in osteogenic differentiation. Immunohistochemistry showed obviously increased expression of CLOCK protein in BMSCs and osteoblasts in N.g MDP–treated mice, but decreased expression in osteocytes. This analytical method provided a basis for the relationship between N.g MDP and remodeling in osteocytes, and the circRNA–miRNA–mRNA triple network may offer a new target for leprosy therapeutics.

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Bioinformatics-Based Identification of a circRNA-miRNA-mRNA Axis in Esophageal Squamous Cell Carcinomas

Journal of Oncology ◽

10.1155/2020/8813800 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Zhaojun Wang ◽

Haifeng Li ◽

Fajun Li ◽

Xin Su ◽

Junhang Zhang ◽

...

Keyword(s):

Squamous Cell ◽

Circular Rna ◽

Gene Expression Omnibus ◽

Differentially Expressed ◽

Messenger Rnas ◽

Disease Symptoms ◽

Protein Protein Interaction ◽

Esophageal Squamous Cell Carcinomas ◽

Microarray Datasets ◽

Important Nodes

Background. Esophageal squamous cell carcinoma (ESCC) has a poor prognosis due to the lack of early disease symptoms. Using bioinformatics tools, this study aimed to discover differentially expressed nonprotein-coding RNAs and genes with potential prognostic relevance in ESCC. Methods. Two microRNAs (miRNAs) and one circular RNA (circRNA) microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differential expression of miRNAs (DEMs) and circRNAs (DECs) was, respectively, identified in ESCC tissue and compared to adjacent healthy tissue. Further analysis was performed using the miRNA microarray datasets, where miRTarBase was used to predict which messenger RNAs (mRNAs) was present. This was followed by protein-protein interaction (PPI) network, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) analyses. Moreover, cytoHubba and UALCAN were used to predict the important nodes and perform patient survival analysis, respectively. The miRNA-associated circRNAs were predicted using the ENCORI website. The interaction between DECs and the predicted circRNAs was also determined. A circRNA-miRNA-mRNA axis was constructed. Results. Associated with RAP1B and circ_0052867, two miRNAs (miR-133b and miR-139-5p) were identified as being differentially expressed and downregulated across the two datasets. Finally, the circ_0052867/miR-139-5p/RAP1B regulatory axis was established. Conclusion. This study provides support for the possible mechanisms of disease progression in ESCC.

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A deletional frameshift mutation in protein 4.2 gene (allele 4.2 Lisboa) associated with hereditary hemolytic anemia

Blood ◽

10.1182/blood.v85.1.250.bloodjournal851250 ◽

1995 ◽

Vol 85 (1) ◽

pp. 250-256 ◽

Cited By ~ 27

Author(s):

S Hayette ◽

D Dhermy ◽

ME dos Santos ◽

M Bozon ◽

D Drenckhahn ◽

...

Keyword(s):

Hemolytic Anemia ◽

Clinical Manifestations ◽

Cell Protein ◽

Nucleotide Sequencing ◽

Red Cell ◽

Western Blots ◽

Exon 2 ◽

Protein 4.2 ◽

Old Portuguese ◽

The Relationship

We studied a 26-year-old Portuguese patient with recessively transmitted hereditary hemolytic anemia. Protein 4.2 was absent from red cell ghosts by Western blotting. Although the 4.2 mRNA was not detected in Northern blots, it was shown to be present by a procedure based on nested reverse transcription-polymerase chain reaction (RT- PCR). Partial nucleotide sequencing disclosed a one-nucleotide deletion at nt 264 (or 265): AAG GTG-->AAG TG, in codon 88 (or 89) belonging to exon 2. This change, defining allele 4.2 Lisboa, placed in frame the nonsense triplet that normally overlaps codons 136 and 137 (GTG ACC). This mutation, which abolishes an EcoNI site, was also found in the gene of the proband (homozygous state), her parents, and her brother (heterozygous state). Apart from anemia, the patient was free of clinical manifestations. Platelet membranes were also investigated using Western blots. Antibodies to red cell protein 4.2 showed a doublet (72 and 70 kD) both in the controls and the patient. This finding raises an interesting question concerning the relationship between this doublet and erythroid protein 4.2.

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Identification of Slc6a19os and SOX11 as Two Novel Essential Genes in Neuropathic Pain Using Integrated Bioinformatic Analysis and Experimental Verification

Frontiers in Neuroscience ◽

10.3389/fnins.2021.627945 ◽

2021 ◽

Vol 15 ◽

Author(s):

Peng Chen ◽

Chen Wang ◽

Dongsheng Lin ◽

Bing Li ◽

Shuai Ye ◽

...

Keyword(s):

Neuropathic Pain ◽

Interaction Network ◽

Essential Genes ◽

Differentially Expressed ◽

Biological Processes ◽

Messenger Rnas ◽

Tissue Development ◽

Western Blots ◽

Qrt Pcr ◽

Non Coding Rnas

The aim of this study was to identify critical genes associated with neuropathic pain. We also used the competing endogenous RNA (ceRNA) hypothesis to identify related long non-coding RNAs (lncRNAs) and messenger RNAs (miRNAs) with potential regulatory roles. We downloaded GSE107180 from the Gene Expression Omnibus database, screened differentially expressed genes (DEGs) using R software, performed comprehensive bioinformatic analyses, and validated the expression of lncRNA Slc6a19os, miR-125a-5p, miR-125b-5p, miR-351-5p, and Sox11 by qRT-PCR and Western blots. We identified 620 DEGs in spared nerve injury (SNI) mice compared with sham (control) mice, including 309 mRNAs and 311 non-coding RNAs. The up-regulated mRNAs were enriched primarily in several inflammation-related GO biological processes and KEGG signaling pathways. A ceRNA network was constructed that included 82 mRNAs, 4 miRNAs, and 2 lnRNAs. An ingenuity pathway analysis (IPA)-based interaction network for mRNAs differentially expressed in the ceRNA identified several biological processes, including “cellular development, connective tissue development and function, tissue development.” Compared with sham mice, lncRNA Slc6a19os and Sox11 expression were significantly up-regulated in dorsal root ganglion (DRG) samples from SNI mice detected using qRT-PCR and Western blots (P < 0.05). MiR-125a-5p, miR-125b-5p, and miR-351-5p expression were down-regulated in DRG samples from SNI mice detected using qRT-PCR (P < 0.05). We concluded that Sox11 and lncRNA Slc6a19os were novel essential genes in the pathogenesis and progression of neuropathic pain and speculated that these two genes were regulated by miR-125a-5p, miR-125b-5p, and miR-351-5p.

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Circular RNA hsa_circ_0000376 Participates in Tumorigenesis of Breast Cancer by Targeting miR-1285-3p

Technology in Cancer Research & Treatment ◽

10.1177/1533033820928471 ◽

2020 ◽

Vol 19 ◽

pp. 153303382092847

Author(s):

Ziqi Peng ◽

Boyang Xu ◽

Feng Jin

Keyword(s):

Breast Cancer ◽

Protein Interaction ◽

Protein Interaction Network ◽

Interaction Network ◽

Circular Rna ◽

Differentially Expressed ◽

Circular Rnas ◽

Messenger Rnas ◽

Protein Protein Interaction ◽

Protein Protein Interaction Network

This study was designed to identify novel circular RNAs and the related regulatory axis to provide research targets for the diagnosis and treatment of breast cancer. The circular RNA expression microarray “GSE101123” related to breast cancer was downloaded from the Gene Expression Omnibus database. The differentially expressed circular RNAs between tumor and normal samples were screened using Limma package. The targeted microRNAs of the differentially expressed circular RNAs and the targeted messenger RNAs of the microRNAs were predicted using miRanda and miRWalk, respectively, and a circular RNAs–microRNAs–messenger RNAs network was constructed. Then, functional enrichment analysis, protein–protein interaction network construction, and drug–gene interaction analysis were conducted for the messenger RNAs. A total of 11 differentially expressed circular RNAs were identified between the breast cancer and normal samples, of which 3 were upregulated, while 8 were downregulated. The circular RNA–microRNA–messenger RNA network contained 1 circular RNA (hsa_circ_0000376), 2 microRNAs (miR-1285-3p and miR-1286), and 353 messenger RNAs. The protein–protein interaction network contained 150 nodes and 240 interactions. The hub genes in the protein–protein interaction network were all targeted messenger RNAs of miR-1285-3p that were significantly enriched in the ubiquitin–proteasome system, apoptosis, cell cycle arrest–related pathways, and cancer-related pathways involving SMAD specific E3 ubiquitin protein ligase 1, β-transducin repeat containing E3 ubiquitin protein ligase, tumor protein P53 among others. Twenty-two drugs were predicted to target 4 messenger RNAs, including tumor protein P53. A novel circular RNA, hsa_circ_0000376, was identified in breast cancer that may act as a sponge targeting miR-1285-3p expression which through its target genes, SMURF1, BTRC, and TP53, may further regulate tumorigenesis.

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Genome-Wide Identification of differently expressed lncRNAs, mRNAs, and circRNAs in patients with osteoarthritis

Current Bioinformatics ◽

10.2174/1574893615999200706002907 ◽

2020 ◽

Vol 15 ◽

Author(s):

Yeqing Sun ◽

Lei Chen ◽

Yingqi Zhang ◽

Jincheng Zhang ◽

Shashi Ranjan Tiwari

Keyword(s):

Regulatory Networks ◽

Expression Profiles ◽

Interleukin 1 ◽

Interaction Network ◽

Circular Rna ◽

Negative Regulation ◽

Differentially Expressed ◽

Positive Regulation ◽

Proteinprotein Interaction ◽

Differently Expressed Genes

Background: Osteoarthritis (OA), one of the most important causes leading to joint disability, was considered as an untreatable disease. A series of genes were reported to regulate the pathogenesis of OA, including microRNAs, Long non-coding RNAs and Circular RNA. So far, the expression profiles and functions of lncRNAs, mRNAs, and circRNAs in OA are not fully understood. Objective: The present study aimed to identify differently expressed genes in OA. Methods: The present study conducted RNA-seq to identify differently expressed genes in OA. Ontology (GO) analysis was used to analysis the Molecular Function and Biological Process. KEGG pathway analysis was used to perform the differentially expressed lncRNAs in biological pathways. Results: Hierarchical clustering revealed a total of 943 mRNAs, 518 lncRNAs, and 300 circRNAs were dysregulated in OA compared to normal samples. Furthermore, we constructed differentially expressed mRNAs mediated proteinprotein interaction network, differentially expressed lncRNAs mediated trans regulatory networks, and competitive endogenous RNA (ceRNA) to reveal the interaction among these genes in OA. Bioinformatics analysis revealed these dysregulated genes were involved in regulating multiple biological processes, such as wound healing, negative regulation of ossification, sister chromatid cohesion, positive regulation of interleukin-1 alpha production, sodium ion transmembrane transport, positive regulation of cell migration, and negative regulation of inflammatory response. To the best of our knowledge, this study for the first time revealed the expression pattern of mRNAs, lncRNAs and circRNAs in OA. Conclusion: This study provided novel information to validate these differentially expressed RNAs may be as possible biomarkers and targets in OA.

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Investigating Diseases and Chemicals in COVID-19 Literature with Text Mining (Preprint)

10.2196/preprints.21503 ◽

2020 ◽

Author(s):

Amir Karami ◽

Brandon Bookstaver ◽

Melissa Nolan

Keyword(s):

Text Mining ◽

Literature Review ◽

Topic Modeling ◽

Large Scale ◽

Clinical Manifestations ◽

International Health ◽

Research Papers ◽

Strategic Plans ◽

Funding Agencies ◽

The Relationship

BACKGROUND The COVID-19 pandemic has impacted nearly all aspects of life and has posed significant threats to international health and the economy. Given the rapidly unfolding nature of the current pandemic, there is an urgent need to streamline literature synthesis of the growing scientific research to elucidate targeted solutions. While traditional systematic literature review studies provide valuable insights, these studies have restrictions, including analyzing a limited number of papers, having various biases, being time-consuming and labor-intensive, focusing on a few topics, incapable of trend analysis, and lack of data-driven tools. OBJECTIVE This study fills the mentioned restrictions in the literature and practice by analyzing two biomedical concepts, clinical manifestations of disease and therapeutic chemical compounds, with text mining methods in a corpus containing COVID-19 research papers and find associations between the two biomedical concepts. METHODS This research has collected papers representing COVID-19 pre-prints and peer-reviewed research published in 2020. We used frequency analysis to find highly frequent manifestations and therapeutic chemicals, representing the importance of the two biomedical concepts. This study also applied topic modeling to find the relationship between the two biomedical concepts. RESULTS We analyzed 9,298 research papers published through May 5, 2020 and found 3,645 disease-related and 2,434 chemical-related articles. The most frequent clinical manifestations of disease terminology included COVID-19, SARS, cancer, pneumonia, fever, and cough. The most frequent chemical-related terminology included Lopinavir, Ritonavir, Oxygen, Chloroquine, Remdesivir, and water. Topic modeling provided 25 categories showing relationships between our two overarching categories. These categories represent statistically significant associations between multiple aspects of each category, some connections of which were novel and not previously identified by the scientific community. CONCLUSIONS Appreciation of this context is vital due to the lack of a systematic large-scale literature review survey and the importance of fast literature review during the current COVID-19 pandemic for developing treatments. This study is beneficial to researchers for obtaining a macro-level picture of literature, to educators for knowing the scope of literature, to journals for exploring most discussed disease symptoms and pharmaceutical targets, and to policymakers and funding agencies for creating scientific strategic plans regarding COVID-19.

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DEBKS: A Tool to Detect Differentially Expressed Circular RNA

Genomics Proteomics & Bioinformatics ◽

10.1016/j.gpb.2021.01.003 ◽

2021 ◽

Author(s):

Zelin Liu ◽

Huiru Ding ◽

Jianqi She ◽

Chunhua Chen ◽

Weiguang Zhang ◽

...

Keyword(s):

Circular Rna ◽

Differentially Expressed

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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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Correlation of Circular RNA hsa_circ_0001946, hsa_circ_0125589, and Environmental Factors With Hypertension

American Journal of Hypertension ◽

10.1093/ajh/hpaa114 ◽

2020 ◽

Vol 33 (11) ◽

pp. 1047-1047

Author(s):

Wan-yue Liu ◽

Yi Sun ◽

Shu-na Huang ◽

Yu-zhen Lin ◽

Hong-yan Guo ◽

...

Keyword(s):

Environmental Factors ◽

Peripheral Blood ◽

Circular Rna ◽

Peripheral Blood Lymphocytes ◽

Normal Weight ◽

Circular Rnas ◽

Blood Leukocytes ◽

Crossover Analysis ◽

History Of ◽

The Relationship

Abstract Background To investigate the main environmental factors of hypertension and the relationship between hypertension and circular RNAs in peripheral blood lymphocytes. Methods This was a case–control study. A total of 681 hypertension patients and 485 subjects without hypertension were recruited between April 2017 and October 2018. All participations completed the questionnaire investigation, physical examination, and laboratory detection. Quantitative real-time polymerase chain reaction was used to analyze circRNAs (hsa_circ_0001946 and hsa_circ_0125589) in peripheral blood leukocytes in 84 hypertensives and 84 controls. Multivariate logistic regression and crossover analysis were used to analyze the interaction and association between environmental factors and circRNAs in hypertension. Results After adjusted by gender, age and marital status, overweight/obesity (odds ratio (OR) = 1.66, 95% confidence interval (CI) 1.24–2.22), abdominal obesity (OR = 2.17, 95% CI 1.54–3.04), anxiety (OR = 2.15, 95% CI 1.41–3.28), family history of hypertension (OR = 4.26, 95% CI 3.18–5.70), and higher levels of hsa_circ_0001946 (OR = 4.13, 95% CI 1.85–9.21) were risk factors for hypertension, while levels of hsa_circ_0125589 were not associated with hypertension. Crossover analysis showed that the risk of hypertension was 13.12 times higher (95% CI 3.89–44.23) in overweight subjects with high hsa_circ_0001946 levels compared with normal weight subjects with low hsa_circ_0001946 levels. Further, the risk of hypertension was 17.78 times higher (95% CI 1.88–168.61) in subjects with anxiety and high hsa_circ_0001946 levels. Conclusions Hypertension is the result of both environmental factors and genetic factors. Higher hsa_circ_0001946 levels, overweight and anxiety may increase the risk of hypertension, while hsa_circ_0125589 levels are not related to hypertension.

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Study on the Relationship between the miRNA-centered ceRNA Regulatory Network and Fatigue

Journal of Molecular Neuroscience ◽

10.1007/s12031-021-01845-3 ◽

2021 ◽

Author(s):

Xingzhe Yang ◽

Feng Li ◽

Jie Ma ◽

Yan Liu ◽

Xuejiao Wang ◽

...

Keyword(s):

Gene Expression ◽

Gene Regulatory Network ◽

Regulatory Network ◽

Hot Spot ◽

Genetic Research ◽

Noncoding Rnas ◽

Messenger Rnas ◽

Effective Prevention ◽

Gene Regulatory ◽

The Relationship

AbstractIn recent years, the incidence of fatigue has been increasing, and the effective prevention and treatment of fatigue has become an urgent problem. As a result, the genetic research of fatigue has become a hot spot. Transcriptome-level regulation is the key link in the gene regulatory network. The transcriptome includes messenger RNAs (mRNAs) and noncoding RNAs (ncRNAs). MRNAs are common research targets in gene expression profiling. Noncoding RNAs, including miRNAs, lncRNAs, circRNAs and so on, have been developed rapidly. Studies have shown that miRNAs are closely related to the occurrence and development of fatigue. MiRNAs can regulate the immune inflammatory reaction in the central nervous system (CNS), regulate the transmission of nerve impulses and gene expression, regulate brain development and brain function, and participate in the occurrence and development of fatigue by regulating mitochondrial function and energy metabolism. LncRNAs can regulate dopaminergic neurons to participate in the occurrence and development of fatigue. This has certain value in the diagnosis of chronic fatigue syndrome (CFS). CircRNAs can participate in the occurrence and development of fatigue by regulating the NF-κB pathway, TNF-α and IL-1β. The ceRNA hypothesis posits that in addition to the function of miRNAs in unidirectional regulation, mRNAs, lncRNAs and circRNAs can regulate gene expression by competitive binding with miRNAs, forming a ceRNA regulatory network with miRNAs. Therefore, we suggest that the miRNA-centered ceRNA regulatory network is closely related to fatigue. At present, there are few studies on fatigue-related ncRNA genes, and most of these limited studies are on miRNAs in ncRNAs. However, there are a few studies on the relationship between lncRNAs, cirRNAs and fatigue. Less research is available on the pathogenesis of fatigue based on the ceRNA regulatory network. Therefore, exploring the complex mechanism of fatigue based on the ceRNA regulatory network is of great significance. In this review, we summarize the relationship between miRNAs, lncRNAs and circRNAs in ncRNAs and fatigue, and focus on exploring the regulatory role of the miRNA-centered ceRNA regulatory network in the occurrence and development of fatigue, in order to gain a comprehensive, in-depth and new understanding of the essence of the fatigue gene regulatory network.

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