Identification and integrated analysis of CircRNA and miRNA of Radiation-Induced lung injury in a mice model

Abstract Radiation-induced lung injury (RILI) is a main threat to patients received thoracic radiotherapy, it is of great importance to understand the molecular mechanism of RILI. Circular RNAs (CircRNAs) have been found to act as the regulator of multiple biological processes and circRNA-miRNA-mRNA axis could play an important role in signaling pathway of many human diseases including radiation injury, here, we first investigate the circRNA and miRNA of radiation-induced lung injury in a mice model. The mice received 12 Gy thoracic irradiation and the irradiated lung tissues at 48 hours after irradiation were analyzed by RNA Sequencing (RNA-seq) technique compared with normal lung tissues. We identified 21 significantly up-regulated while significantly 33 down-regulated miRNAs. Among 27 differentially expressed circRNAs, 10 were down-regulated and 17 were up-regulated. We then performed circRNAs GO analysis of the target mRNAs of these significantly differently expressed circRNAs. These differentially expressed miRNAs took part in series of cellular processes such as positive regulation of alpha-beta T cell proliferation, interstitial matrix, collagen fibril organization, chemokine receptor activity, cellular defense response, and B cell receptor signaling pathway. Through this study, we found that immune-related molecular pathways play an important role in the early response after radiotherapy. In the future, research on the target mechanism and early intervention of circRNAs with associated miRNAs will benefit the treatment of RILI.

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Integrated Analysis of circRNA-miRNA-mRNA Regulatory Networks in the Intestine of Sebastes schlegelii Following Edwardsiella tarda Challenge

Frontiers in Immunology ◽

10.3389/fimmu.2020.618687 ◽

2021 ◽

Vol 11 ◽

Author(s):

Min Cao ◽

Xu Yan ◽

Baofeng Su ◽

Ning Yang ◽

Qiang Fu ◽

...

Keyword(s):

Signaling Pathways ◽

Signaling Pathway ◽

Regulatory Networks ◽

Target Genes ◽

Differentially Expressed ◽

Edwardsiella Tarda ◽

Circular Rnas ◽

Integrated Analysis ◽

Apoptosis Pathway ◽

Sebastes Schlegelii

Sebastes schlegelii, an important aquaculture species, has been widely cultured in East Asian countries. With the increase in the cultivation scale, various diseases have become major threats to the industry. Evidence has shown that non-coding RNAs (ncRNAs) have remarkable functions in the interactions between pathogens and their hosts. However, little is known about the mechanisms of circular RNAs (circRNAs) and coding RNAs in the process of preventing pathogen infection in the intestine in teleosts. In this study, we aimed to uncover the global landscape of mRNAs, circRNAs, and microRNAs (miRNAs) in response to Edwardsiella tarda infection at different time points (0, 2, 6, 12, and 24 h) and to construct regulatory networks for exploring the immune regulatory mechanism in the intestine of S. schlegelii. In total, 1,794 mRNAs, 87 circRNAs, and 79 miRNAs were differentially expressed. The differentially expressed RNAs were quantitatively validated using qRT-PCR. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that most of the differentially expressed mRNA genes and the target genes of ncRNAs were related to immune signaling pathways, such as the NF-κB signal pathway, pathogen recognition receptors related to signaling pathways (Toll-like receptors and Nod-like receptors), and the chemokine signaling pathway. Based on these differentially expressed genes, 624 circRNA-miRNA pairs and 2,694 miRNA-mRNA pairs were predicted using the miRanda software. Integrated analyses generated 25 circRNA-miRNA-mRNA interaction networks. In a novel_circ_0004195/novel-530/IκB interaction network, novel_530 was upregulated, while its two targets, novel_circ_0004195 and IκB, were downregulated after E. tarda infection. In addition, two circRNA-miRNA-mRNA networks related to apoptosis (novel_circ_0003210/novel_152/apoptosis-stimulating of p53 protein 1) and interleukin (novel_circ_0001907/novel_127/interleukin-1 receptor type 2) were also identified in our study. We thus speculated that the downstream NF-κB signaling pathway, p53 signaling pathway, and apoptosis pathway might play vital roles in the immune response in the intestine of S. schlegelii. This study revealed a landscape of RNAs in the intestine of S. schlegelii during E. tarda infection and provided clues for further study on the immune mechanisms and signaling networks based on the circRNA-miRNA-mRNA axis in S. schlegelii.

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Inhibition of Rac1 attenuates radiation-induced lung injury while suppresses lung tumor in mice

Cell Death Discovery ◽

10.1038/s41420-021-00791-8 ◽

2022 ◽

Vol 8 (1) ◽

Author(s):

Ni An ◽

Zhenjie Li ◽

Xiaodi Yan ◽

Hainan Zhao ◽

Yajie Yang ◽

...

Keyword(s):

Ionizing Radiation ◽

Lung Injury ◽

Mouse Model ◽

Tumor Cells ◽

Nuclear Translocation ◽

Lung Tumor ◽

Lung Epithelial Cells ◽

Normal Lung ◽

Limiting Factor ◽

Radiation Induced

AbstractThe lung is one of the most sensitive tissues to ionizing radiation, thus, radiation-induced lung injury (RILI) stays a key dose-limiting factor of thoracic radiotherapy. However, there is still little progress in the effective treatment of RILI. Ras-related C3 botulinum toxin substrate1, Rac1, is a small guanosine triphosphatases involved in oxidative stress and apoptosis. Thus, Rac1 may be an important molecule that mediates radiation damage, inhibition of which may produce a protective effect on RILI. By establishing a mouse model of radiation-induced lung injury and orthotopic lung tumor-bearing mouse model, we detected the role of Rac1 inhibition in the protection of RILI and suppression of lung tumor. The results showed that ionizing radiation induces the nuclear translocation of Rac1, the latter then promotes nuclear translocation of P53 and prolongs the residence time of p53 in the nucleus, thereby promoting the transcription of Trp53inp1 which mediates p53-dependent apoptosis. Inhibition of Rac1 significantly reduce the apoptosis of normal lung epithelial cells, thereby effectively alleviating RILI. On the other hand, inhibition of Rac1 could also significantly inhibit the growth of lung tumor, increase the radiation sensitivity of tumor cells. These differential effects of Rac1 inhibition were related to the mutation and overexpression of Rac1 in tumor cells.

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Proteomic Analysis of Radiation-Induced Acute Liver Damage in a Rabbit Model

Dose-Response ◽

10.1177/1559325819889508 ◽

2019 ◽

Vol 17 (4) ◽

pp. 155932581988950 ◽

Cited By ~ 1

Author(s):

Lingong Jiang ◽

Huimin Jia ◽

Zhicheng Tang ◽

Xiaofei Zhu ◽

Yangsen Cao ◽

...

Keyword(s):

Signaling Pathway ◽

Liver Damage ◽

Rabbit Model ◽

Mapk Signaling ◽

Differentially Expressed ◽

Mitogen Activated Protein Kinase ◽

Differentially Expressed Proteins ◽

Label Free ◽

Radiation Induced ◽

Liver Tissues

Radiation-induced liver damage (RILD) has become a limitation in radiotherapy for hepatocellular carcinoma. We established a rabbit model of RILD by CyberKnife. Electron microscopy analysis revealed obvious nuclear atrophy and disposition of fat in the nucleus after irradiation. We then utilized a mass spectrometry-based label-free relative quantitative proteomics approach to compare global proteomic changes of rabbit liver in response to radiation. In total, 2365 proteins were identified, including 338 proteins that were significantly dysregulated between irradiated and nonirradiated liver tissues. These differentially expressed proteins included USP47, POLR2A, CSTB, MCFD2, and CSNK2A1. Real-time polymerase chain reaction confirmed that USP47 and CABLES1 transcripts were significantly higher in irradiated liver tissues, whereas MCFD2 and CSNK2A1 expressions were significantly reduced. In Clusters of Orthologous Groups of proteins analysis, differentially expressed proteins were annotated and divided into 24 categories, including posttranslational modification, protein turnover, and chaperones. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the enriched pathways in dysregulated proteins included the vascular endothelial growth factors (VEGF) signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, and the adipocytokine signaling pathway. The identification of proteins and pathways is crucial toward elucidating the radiation response process of the liver, which may facilitate the discovery of novel therapeutic targets.

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Integrated analysis of autophagy-related genes(ATGs) reveals the prognostic value of oral squamous cell carcinoma

10.21203/rs.3.rs-17099/v1 ◽

2020 ◽

Author(s):

Guangzhao Huang ◽

Zhi-yun Li ◽

Yu Rao ◽

Xiao-zhi Lv

Keyword(s):

Survival Analysis ◽

Signaling Pathway ◽

Risk Score ◽

Prognostic Value ◽

Risk Model ◽

Cox Regression ◽

Expression Profiles ◽

Differentially Expressed ◽

Integrated Analysis ◽

Score Model

Abstract Background: Increasing evidence demonstrated that autophagy paly a crucial role in initiation and progression of OSCC. The aim of this study was to explore the prognostic value of autophagy-related genes(ATGs) in patients with OSCC. RNA-seq and clinical data were downloaded from TCGA database following extrating ATGs expression profiles. Then, differentially expressed analysis was performed in R software EdgeR package, and the potential biological function of differentially expressed ATGs were explored by GO and KEGG enrichment analysis. Furthermore, a risk score model based on ATGs was constructed to predict the overall survival. Moreover, univariate, multivariate cox regression and survival analysis were used to select autophagy related biomarkers which were identified by RT-qPCR in OSCC cell lines, OSCC tissues and matched normal mucosal tissues. Results: Total of 232 ATGs were extrated and 37 genes were differentially expressed in OSCC. GO and KEGG analysis indicated that these differentially expressed genes were mainly located in autophagosome membrane, and associated with apoptosis, platinum drug resistance, ErbB signaling pathway and TNF signaling pathway. Furthermore, a risk score model including 9 variables was constructed and subsequently identified with univariate, multivariate cox regression, survival analysis and Receiver Operating Characteristic curve(ROC). Moreover, ATG12 and BID were identified as potential autophagy related biomakers. Conclusion: This study successfully constructed a risk model to predict the prognosis of patients with OSCC, and the risk score may be as a independent prognostic biomarker in OSCC. ATG12 and BID were identified as potential biomarkers in tumor diagnosis and treatment of OSCC.

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Comparative adipose transcriptome analysis digs out genes related to fat deposition in two pig breeds

Scientific Reports ◽

10.1038/s41598-019-49548-5 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Kai Xing ◽

Kejun Wang ◽

Hong Ao ◽

Shaokang Chen ◽

Zhen Tan ◽

...

Keyword(s):

Candidate Genes ◽

Signaling Pathway ◽

Meat Quality ◽

Differentially Expressed Genes ◽

Molecular Mechanisms ◽

Mapk Signaling ◽

Fat Deposition ◽

Differentially Expressed ◽

Integrated Analysis ◽

Pig Breeds

Abstract Fatness traits are important in pigs because of their implications for fattening efficiency, meat quality, reproductive performance and immunity. Songliao black pigs and Landrace pigs show important differences in production and meat quality traits, including fatness and muscle growth. Therefore, we used a high-throughput massively parallel RNA-seq approach to identify genes differentially expressed in backfat tissue between these two breeds (six pigs in each). An average of 37.87 million reads were obtained from the 12 samples. After statistical analysis of gene expression data by edgeR, a total of 877 differentially expressed genes were detected between the two pig breeds, 205 with higher expression and 672 with lower expression in Songliao pigs. Candidate genes (LCN2, CES3, DGKB, OLR1, LEP, PGM1, PCK1, ACACB, FADS1, FADS2, MOGAT2, SREBF1, PPARGC1B) with known effects on fatness traits were included among the DEGs. A total of 1071 lncRNAs were identified, and 85 of these lncRNAs were differentially expressed, including 53 up-regulated and 32 down-regulated lncRNAs, respectively. The differentially expressed genes and lncRNAs involved in glucagon signaling pathway, glycolysis/gluconeogenesis, insulin signaling pathway, MAPK signaling pathway and so on. Integrated analysis potential trans-regulating or cis-regulating relation between DEGs and DE lncRNAs, suggested lncRNA MSTRG.2479.1 might regulate the expressed level of VLDLR affecting porcine fat metabolism. These results provide a number of candidate genes and lncRNAs potentially involved in porcine fat deposition and provide a basis for future research on the molecular mechanisms underlying in fat deposition.

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Bioinformatics Analysis of Key Genes and circRNA-miRNA-mRNA Regulatory Network in Gastric Cancer

BioMed Research International ◽

10.1155/2020/2862701 ◽

2020 ◽

Vol 2020 ◽

pp. 1-16 ◽

Cited By ~ 1

Author(s):

Yiting Tian ◽

Yang Xing ◽

Zheng Zhang ◽

Rui Peng ◽

Luyu Zhang ◽

...

Keyword(s):

Gastric Cancer ◽

Extracellular Matrix ◽

Expression Profiles ◽

Gene Expression Omnibus ◽

Differentially Expressed ◽

Receptor Interaction ◽

Future Research ◽

Circular Rnas ◽

Ppi Network ◽

Protein Protein Interaction

Gastric cancer (GC) is one of the most common malignancies in the world, with morbidity and mortality ranking second among all cancers. Accumulating evidences indicate that circular RNAs (circRNAs) are closely correlated with tumorigenesis. However, the mechanisms of circRNAs still remain unclear. This study is aimed at determining hub genes and circRNAs and analyzing their potential biological functions in GC. Expression profiles of mRNAs and circRNAs were downloaded from the Gene Expression Omnibus (GEO) data sets of GC and paracancer tissues. Differentially expressed genes (DEGs) and differentially expressed circRNAs (DE-circRNAs) were identified. The target miRNAs of DE-circRNAs and the bidirectional interaction between target miRNAs and DEGs were predicted. Functional analysis was performed, and the protein-protein interaction (PPI) network and the circRNA-miRNA-mRNA network were established. A total of 456 DEGs and 2 DE-circRNAs were identified with 3 mRNA expression profiles and 2 circRNA expression profiles. GO analysis indicated that DEGs were mainly enriched in extracellular matrix and cell adhesion, and KEGG confirmed that DEGs were mainly associated with focal adhesion, the PI3K-Akt signaling pathway, extracellular matrix- (ECM)- receptor interaction, and gastric acid secretion. 15 hub DEGs (BGN, COL1A1, COL1A2, FBN1, FN1, SPARC, SPP1, TIMP1, UBE2C, CCNB1, CD44, CXCL8, COL3A1, COL5A2, and THBS1) were identified from the PPI network. Furthermore, the survival analysis indicate that GC patients with a high expression of the following 9 hub DEGs, namely, BGN, COL1A1, COL1A2, FBN1, FN1, SPARC, SPP1, TIMP1, and UBE2C, had significantly worse overall survival. The circRNA-miRNA-mRNA network was constructed based on 1 circRNA, 15 miRNAs, and 45 DEGs. In addition, the 45 DEGs included 5 hub DEGs. These results suggested that hub DEGs and circRNAs could be implicated in the pathogenesis and development of GC. Our findings provide novel evidence on the circRNA-miRNA-mRNA network and lay the foundation for future research of circRNAs in GC.

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Identification of potential microRNAs and KEGG pathways in denervation muscle atrophy based on meta-analysis

Scientific Reports ◽

10.1038/s41598-021-92489-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Xinyi Gu ◽

Bo Jin ◽

Zhidan Qi ◽

Xiaofeng Yin

Keyword(s):

Signaling Pathway ◽

Muscle Atrophy ◽

Meta Analysis ◽

Cell Receptor ◽

Differentially Expressed ◽

Receptor Signaling ◽

Denervated Muscle ◽

Kegg Pathways ◽

Receptor Signaling Pathway ◽

Cell Receptor Signaling

AbstractThe molecular mechanism of muscle atrophy has been studied a lot, but there is no comprehensive analysis focusing on the denervated muscle atrophy. The gene network that controls the development of denervated muscle atrophy needs further elucidation. We examined differentially expressed genes (DEGs) from five denervated muscle atrophy microarray datasets and predicted microRNAs that target these DEGs. We also included the differentially expressed microRNAs datasets of denervated muscle atrophy in previous studies as background information to identify potential key microRNAs. Finally, we compared denervated muscle atrophy with disuse muscle atrophy caused by other reasons, and obtained the Den-genes which only differentially expressed in denervated muscle atrophy. In this meta-analysis, we obtained 429 up-regulated genes, 525 down-regulated genes and a batch of key microRNAs in denervated muscle atrophy. We found eight important microRNA-mRNA interactions (miR-1/Jun, miR-1/Vegfa, miR-497/Vegfa, miR-23a/Vegfa, miR-206/Vegfa, miR-497/Suclg1, miR-27a/Suclg1, miR-27a/Mapk14). The top five KEGG pathways enriched by Den-genes are Insulin signaling pathway, T cell receptor signaling pathway, MAPK signaling pathway, Toll-like receptor signaling pathway and B cell receptor signaling pathway. Our research has delineated the RNA regulatory network of denervated muscle atrophy, and uncovered the specific genes and terms in denervated muscle atrophy.

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Key circular RNAs identified in male osteoporosis patients by whole transcriptome sequencing

PeerJ ◽

10.7717/peerj.11420 ◽

2021 ◽

Vol 9 ◽

pp. e11420

Author(s):

Haijin Zhang ◽

Xue Song ◽

Zongyan Teng ◽

Sujun Cheng ◽

Weigang Yu ◽

...

Keyword(s):

Signaling Pathway ◽

Expression Profile ◽

Systemic Disease ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Male Osteoporosis ◽

Circular Rnas ◽

Healthy Controls ◽

Regulation Of Cell Cycle ◽

Whole Transcriptome

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.

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Integrated Analysis of a circRNA-miRNA-mRNA Axis in Intervertebral Disc Degeneration

10.21203/rs.3.rs-129853/v1 ◽

2020 ◽

Author(s):

Laifu Wei ◽

Bizhi Tu ◽

Fei Gao ◽

Jun Qian

Keyword(s):

Intervertebral Disc ◽

Disc Degeneration ◽

Intervertebral Disc Degeneration ◽

Underlying Mechanism ◽

Differentially Expressed ◽

Circular Rnas ◽

Integrated Analysis ◽

Control Group ◽

Common Symptom ◽

Sequencing Data

Abstract Background: Low back pain (LBP) is a common symptom in daily life and one of the primary causes is intervertebral disc degeneration (IDD). Growing studies have indicated that circular RNAs (circRNAs) are intimately associated with IDD; however, the underlying mechanism has not yet been elucidated. We aimed to explore how circRNAs regulate IDD in an effort to provide novel insight for clinical diagnosis and treatment. Methods: The sequencing data of circRNAs, microRNAs (miRNAs), and mRNA were acquired from Gene Expression Omnibus (GEO) datasets. By analyzing the dataset consisting of a control group and degenerated group, differentially expressed circRNAs, miRNAs, and mRNAs were collected, and then the intersection of circRNAs, miRNAs, and mRNAs was screened. According to these intersectional RNAs, we constructed an integrally circRNA-miRNA-mRNA network. Finally, using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, we further clarified functions of the intersectional mRNA in IDD. Results: we obtained 620 differentially expressed circRNAs(DEcircRNAs), 13 miRNA (DEmiRNA), 273 mRNAs(DEmRNAs), 12 intersectional miRNAs, and 47 intersectional mRNAs. Finally, based on interactional 8 circRNA, 5 miRNAs and 15 mRNAs, an integrally circRNA-miRNA-mRNA network was constructed. Eight circRNAs, contained hsa_circ_0032254, hsa_circ_0003183, hsa_circ_0032253, hsa_circ_0001293, hsa_circ_0004565, hsa_circ_0091570, hsa_circ_0077526, and hsa_circ_0057552, may regulate IDD onset and progression by acting as competing endogenous RNAs. The results of GO and KEGG analyses implied that the targeted genes might significantly correlate to IDD.Conclusion: our findings improved a better understanding of the circRNA-related ceRNA regulatory mechanism in IDD and offered possible targets for IDD treatment.

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Screening for differentially expressed circRNAs in ischemic stroke by RNA sequencing

BMC Neurology ◽

10.1186/s12883-021-02397-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Duncan Wei ◽

Jian Chen ◽

Xiaopu Chen ◽

Shaoyan Wu ◽

Zhaolin Chen ◽

...

Keyword(s):

Ischemic Stroke ◽

Signaling Pathway ◽

Rna Sequencing ◽

Cell Receptor ◽

Differentially Expressed ◽

Receptor Signaling ◽

Qrt Pcr ◽

Receptor Signaling Pathway ◽

Cell Receptor Signaling ◽

Host Genes

Abstract Background Ischemic stroke is a disease with high rate of death and disability worldwide. CircRNAs, as a novel type of non-coding RNAs, lacking 5’ caps and 3’ poly-A tails, has been associated with ischemic stroke. This study aimed to investigate key circRNAs related to ischemic stroke. Methods RNA sequencing was performed obtain the circRNA expression profiles from peripheral whole blood of three ischemic stroke patients and three healthy individuals. Through bioinformatic analysis, differentially expressed circRNAs (DEcircRNAs) were identified, and GO and pathway analyses for the host genes of DEcircRNAs were conducted. The expression levels of selected circRNAs were analyzed with qRT-PCR. To further explore the functions of key circRNAs, a DEcircRNA-miRNA interaction network was constructed. Results A total of 736 DEcircRNAs were detected in ischemic stroke. Functional annotation of host genes of DEcircRNAs revealed several significantly enriched pathways, including Fc epsilon RI signaling pathway, B cell receptor signaling pathway, and T cell receptor signaling pathway. The qRT-PCR results were largely in keeping with our RNA-seq data. The ROC curve analyses indicated that hsa_circ_0000745, hsa_circ_0001459, hsa_circ_0003694 and hsa_circ_0007706 with relatively high diagnostic value. A circRNA-miRNA network, including 1544 circRNA-miRNA pairs, 456 circRNAs and 4 miRNAs, was obtained. Conclusions The results of our study may help to elucidate the specific mechanism underlying ischemic stroke.

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