scholarly journals Deep Sequencing of the Rat MCAO Cortexes Reveals Crucial circRNAs Involved in Early Stroke Events and Their Regulatory Networks

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Chengtan Wang ◽  
Yuying Yang ◽  
Mengsi Xu ◽  
Fuxiu Mao ◽  
Peng Yang ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Deep Sequencing ◽  
Posttranscriptional Regulation ◽  
Regulatory Networks ◽  
Target Genes ◽  
Interaction Network ◽  
Artery Occlusion ◽  
Circular Rnas ◽  
Sprague Dawley ◽  
Downstream Target

Circular RNAs (circRNAs) are highly enriched in the central nervous system and significantly involved in a range of brain-related physiological and pathological processes. Ischemic stroke is a complex disorder caused by multiple factors; however, whether brain-derived circRNAs participate in the complex regulatory networks involved in stroke pathogenesis remains unknown. Here, we successfully constructed a cerebral ischemia-injury model of middle cerebral artery occlusion (MCAO) in male Sprague-Dawley rats. Preliminary qualitative and quantitative analyses of poststroke cortical circRNAs were performed through deep sequencing, and RT-PCR and qRT-PCR were used for validation. Of the 24,858 circRNAs expressed in the rat cerebral cortex, 294 circRNAs were differentially expressed in the ipsilateral cerebral cortex between the MCAO and sham rat groups. Cluster, GO, and KEGG analyses showed enrichments of these circRNAs and their host genes in numerous biological processes and pathways closely related to stroke. We selected 106 of the 294 circRNAs and constructed a circRNA-miRNA-mRNA interaction network comprising 577 sponge miRNAs and 696 target mRNAs. In total, 15 key potential circRNAs were predicted to be involved in the posttranscriptional regulation of a series of downstream target genes, which are widely implicated in poststroke processes, such as oxidative stress, apoptosis, inflammatory response, and nerve regeneration, through the competing endogenous RNA mechanism. Thus, circRNAs appear to be involved in multilevel actions that regulate the vast network of multiple mechanisms and events that occur after a stroke. These results provide novel insights into the complex pathophysiological mechanisms of stroke.

scholarly journals Epigenetic Associations between lncRNA/circRNA and miRNA in Hepatocellular Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2622 ◽  
Author(s):  
Tae-Su Han ◽  
Keun Hur ◽  
Hyun-Soo Cho ◽  
Hyun Seung Ban
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regulatory Networks ◽  
Epithelial To Mesenchymal Transition ◽  
Target Genes ◽  
Circular Rnas ◽  
Cancer Cell Growth ◽  
Mesenchymal Transition ◽  
Downstream Target ◽  
Non Coding Rnas ◽  
Regulation Model

The three major members of non-coding RNAs (ncRNAs), named microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play an important role in hepatocellular carcinoma (HCC) development. Recently, the competing endogenous RNA (ceRNA) regulation model described lncRNA/circRNA as a sponge for miRNAs to indirectly regulate miRNA downstream target genes. Accumulating evidence has indicated that ceRNA regulatory networks are associated with biological processes in HCC, including cancer cell growth, epithelial to mesenchymal transition (EMT), metastasis, and chemoresistance. In this review, we summarize recent discoveries, which are specific ceRNA regulatory networks (lncRNA/circRNA-miRNA-mRNA) in HCC and discuss their clinical significance.

scholarly journals Identification of hub driving genes and regulators of lung adenocarcinoma based on the gene Co-expression network

2020 ◽  
Vol 40 (4) ◽  
Author(s):  
Zihao Xu ◽  
Zilong Wu ◽  
Jiatang Xu ◽  
Jingtao Zhang ◽  
Bentong Yu
Keyword(s):  
Lung Adenocarcinoma ◽  
Target Genes ◽  
Characteristic Curve ◽  
Interaction Network ◽  
Mapk Signaling ◽  
The Cancer Genome Atlas ◽  
Circular Rnas ◽  
Node Degree ◽  
Protein Protein Interaction ◽  
Cancer Tissues

Abstract Lung adenocarcinoma (LUAD) remains the leading cause of cancer-related deaths worldwide. Increasing evidence suggests that circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) can regulate target gene expression and participate in tumor genesis and progression. However, hub driving genes and regulators playing a potential role in LUAD progression have not been fully elucidated yet. Based on data from The Cancer Genome Atlas database, 2837 differentially expressed genes, 741 DE-regulators were screened by comparing cancer tissues with paracancerous tissues. Then, 651 hub driving genes were selected by the topological relation of the protein–protein interaction network. Also, the target genes of DE-regulators were identified. Moreover, a key gene set containing 65 genes was obtained from the hub driving genes and target genes intersection. Subsequently, 183 hub regulators were selected based on the analysis of node degree in the ceRNA network. Next, a comprehensive analysis of the subgroups and Wnt, mTOR, and MAPK signaling pathways was conducted to understand enrichment of the subgroups. Survival analysis and a receiver operating characteristic curve analysis were further used to screen for the key genes and regulators. Furthermore, we verified key molecules based on external database, LRRK2, PECAM1, EPAS1, LDB2, and HOXA11-AS showed good results. LRRK2 was further identified as promising biomarker associated with CNV alteration and various immune cells’ infiltration levels in LUAD. Overall, the present study provided a novel perspective and insight into hub driving genes and regulators in LUAD, suggesting that the identified signature could serve as an independent prognostic biomarker.

scholarly journals Commensal microbiota drive the functional diversification of colon macrophages

2019 ◽  
Vol 13 (2) ◽  
pp. 216-229 ◽  
Author(s):  
Byunghyun Kang ◽  
Luigi J. Alvarado ◽  
Teayong Kim ◽  
Michael L. Lehmann ◽  
Hyeseon Cho ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Target Genes ◽  
Myeloid Cell ◽  
Mononuclear Phagocytes ◽  
Developmental Pathways ◽  
Functional Diversification ◽  
Downstream Target ◽  
Commensal Microbiota ◽  
Specific Pathogen ◽  
Gene Regulatory

AbstractMononuclear phagocytes are a heterogeneous population of leukocytes essential for immune homeostasis that develop tissue-specific functions due to unique transcriptional programs driven by local microenvironmental cues. Single cell RNA sequencing (scRNA-seq) of colonic myeloid cells from specific pathogen free (SPF) and germ-free (GF) C57BL/6 mice revealed extensive heterogeneity of both colon macrophages (MPs) and dendritic cells (DCs). Modeling of developmental pathways combined with inference of gene regulatory networks indicate two major trajectories from common CCR2+ precursors resulting in colon MP populations with unique transcription factors and downstream target genes. Compared to SPF mice, GF mice had decreased numbers of total colon MPs, as well as selective proportional decreases of two major CD11c+CD206intCD121b+ and CD11c−CD206hiCD121b− colon MP populations, whereas DC numbers and proportions were not different. Importantly, these two major colon MP populations were clearly distinct from other colon MP populations regarding their gene expression profile, localization within the lamina propria (LP) and ability to phagocytose macromolecules from the blood. These data uncover the diversity of intestinal myeloid cell populations at the molecular level and highlight the importance of microbiota on the unique developmental as well as anatomical and functional fates of colon MPs.

scholarly journals The Biological Role of Sponge Circular RNAs in Gastric Cancer: Main Players or Coadjuvants?

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1982
Author(s):  
Adenilson Leão Pereira ◽  
Leandro Magalhães ◽  
Rafael Pompeu Pantoja ◽  
Gilderlanio Araújo ◽  
Ândrea Ribeiro-dos-Santos ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Target Genes ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Interaction Network ◽  
Gastric Carcinogenesis ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Circular Rnas ◽  
Cancer Genome Atlas

Circular RNAs (circRNAs) are a new class of long noncoding RNAs able to perform multiple functions, including sponging microRNAs (miRNAs) and RNA-Binding Proteins (RBPs). They play an important role in gastric carcinogenesis, but its involvement during gastric cancer (GC) development and progression are not well understood. We gathered miRNA and/or RBPs sponge circRNAs present in GC, and accessed their biological roles through functional enrichment of their target genes or ligand RBPs. We identified 54 sponge circRNAs in GC that are able to sponge 51 miRNAs and 103 RBPs. Then, we evaluated their host gene expression using The Cancer Genome Atlas (TCGA) database and observed that COL1A2 is the most overexpressed gene, which may be due to circHIPK3/miR-29b-c/COL1A2 axis dysregulation. We identified 27 GC-related pathways that may be affected mainly by circPVT1, circHIPK3 and circNF1. Our results indicate that circHIPK3/miR-107/BDNF/LIN28 axis may mediate chemoresistance in GC, and that circPVT1, circHIPK3, circNF1, ciRS-7 and circ_0000096 appear to be involved in gastrointestinal cancer development. Lastly, circHIPK3, circNRIP1 and circSMARCA5 were identified in different ethnic populations and may be ubiquitous modulators of gastric carcinogenesis. Overall, the studied sponge circRNAs are part of a complex RBP-circRNA-miRNA-mRNA interaction network, and are involved in the establishment, chemoresistance and progression of GC.

scholarly journals NOD-Like Receptor Signaling in Cholesteatoma

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Anke Leichtle ◽  
Christin Klenke ◽  
Joerg Ebmeyer ◽  
Markus Daerr ◽  
Karl-Ludwig Bruchhage ◽  
...  
Keyword(s):  
Target Genes ◽  
Interaction Network ◽  
Innate Immune ◽  
Downstream Target ◽  
Innate Immune Signaling ◽  
Intracranial Complications ◽  
Ear Infections ◽  
Target Molecules ◽  
Altered Regulation

Background. Cholesteatoma is a destructive process of the middle ear resulting in erosion of the surrounding bony structures with consequent hearing loss, vestibular dysfunction, facial paralysis, or intracranial complications. The etiopathogenesis of cholesteatoma is controversial but is associated with recurrent ear infections. The role of intracellular innate immune receptors, the NOD-like receptors, and their associated signaling networks was investigated in cholesteatoma, since mutations in NOD-like receptor-related genes have been implicated in other chronic inflammatory disorders.Results. The expression of NOD2 mRNA and protein was significantly induced in cholesteatoma compared to the external auditory canal skin, mainly located in the epithelial layer of cholesteatoma. Microarray analysis showed significant upregulation for NOD2, not for NOD1, TLR2, or TLR4 in cholesteatoma. Moreover, regulation of genes in an interaction network of the NOD-adaptor molecule RIPK2 was detected. In addition to NOD2, NLRC4, and PYCARD, the downstream molecules IRAK1 and antiapoptotic regulator CFLAR showed significant upregulation, whereas SMAD3, a proapoptotic inducer, was significantly downregulated. Finally, altered regulation of inflammatory target genes of NOD signaling was detected.Conclusions. These results indicate that the interaction of innate immune signaling mediated by NLRs and their downstream target molecules is involved in the etiopathogenesis and growth of cholesteatoma.

scholarly journals Identification of circRNA–miRNA–mRNA networks contributes to explore underlying pathogenesis and therapy strategy of gastric cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhijie Dong ◽  
Zhaoyu Liu ◽  
Min Liang ◽  
Jinhui Pan ◽  
Mingzhen Lin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Target Genes ◽  
Trichostatin A ◽  
Quantitative Polymerase Chain Reaction ◽  
Human Tumor ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Circular Rnas ◽  
Therapy Strategy

Abstract Background Circular RNAs (circRNAs) are a new class of noncoding RNAs that have gained increased attention in human tumor research. However, the identification and function of circRNAs are largely unknown in the context of gastric cancer (GC). This study aims to identify novel circRNAs and determine their action networks in GC. Methods A comprehensive strategy of data mining, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and computational biology were conducted to discover novel circRNAs and to explore their potential mechanisms in GC. Promising therapeutic drugs for GC were determined by connectivity map (CMap) analysis. Results Six overlapped differentially expressed circRNAs (DECs) were screened from selected microarray and RNA-Seq datasets of GC, and the six DECs were then validated by sanger sequencing and RNase R treatment. Subsequent RT-qPCR analysis of GC samples confirmed decreased expressions of the six DECs (hsa_circ_0000390, hsa_circ_0000615, hsa_circ_0001438, hsa_circ_0002190, hsa_circ_0002449 and hsa_circ_0003120), all of which accumulated preferentially in the cytoplasm. MiRNA binding sites and AGO2 occupation of the six circRNAs were predicted using online databases, and circRNA–miRNA interactions including the six circRNAs and 33 miRNAs were determined. Then, 5320 target genes of the above 33 miRNAs and 1492 differently expressed genes (DEGs) from The Cancer Genome Atlas (TCGA) database were identified. After intersecting the miRNA target genes and the 889 downregulated DEGs, 320 overlapped target genes were acquired. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that these target genes were related to two critical tumor-associated signaling pathways. A protein–protein interaction network with the 320 target genes was constructed using STRING, and fifteen hubgenes (ATF3, BTG2, DUSP1, EGR1, FGF2, FOSB, GNAO1, GNAI1, GNAZ, GNG7, ITPR1, ITPKB, JUND, NR4A3, PRKCB) in the network were identified. Finally, bioactive chemicals (including vorinostat, trichostatin A and astemizole) based on the fifteen hubgenes were identifed as therapeutic agents for GC through the CMap analysis. Conclusions This study provides a novel insight for further exploration of the pathogenesis and therapy of GC from the circRNA-miRNA-mRNA network perspective.

scholarly journals Identification of Differentially Expressed Non-coding RNA Networks With Potential Immunoregulatory Roles During Salmonella Enteritidis Infection in Ducks

2021 ◽  
Vol 8 ◽  
Author(s):  
Yu Zhang ◽  
Xiaoqian Dong ◽  
Lie Hou ◽  
Zhengfeng Cao ◽  
Guoqiang Zhu ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Regulatory Networks ◽  
Egg Production ◽  
Salmonella Enteritidis ◽  
Time Course ◽  
Target Genes ◽  
Differentially Expressed ◽  
Receptor Interaction ◽  
Circular Rnas ◽  
Preovulatory Follicles

Salmonella enterica serovar Enteritidis (S. Enteritidis) is a pathogen that can colonize the preovulatory follicles of poultry, thereby causing both reduced egg production and an elevated risk of foodborne salmonellosis in humans. Although a few studies have revealed S. Enteritidis preferentially invades the granulosa cell layer within these follicles, it can readily persist and proliferate through mechanisms that are not well-understood. In this study, we characterized competing endogenous RNA (ceRNA) regulatory networks within duck granulosa cells following time-course of S. Enteritidis challenge. The 8108 long non-coding RNAs (lncRNAs), 1545 circular RNAs (circRNAs), 542 microRNAs (miRNAs), and 4137 mRNAs (fold change ≥2; P < 0.01) were differentially expressed during S. Enteritidis challenge. Also, eight mRNAs, eight lncRNAs and five circRNAs were selected and the consistent expression trend was found between qRT-PCR detection and RNA-seq. Moreover, the target genes of these differentially expressed ncRNAs (including lncRNAs, circRNAs and miRNAs) were predicted, and significantly enriched in the innate immune response and steroidogenesis pathways. Then, the colocalization and coexpression analyses were conducted to investigate relationships between ncRNAs and mRNAs. The 16 differentially expressed miRNAs targeting 60 differentially expressed mRNAs were identified in granulosa cells at 3 and 6 h post-infection (hpi) and enriched in the MAPK, GnRH, cytokine-cytokine receptor interaction, Toll-like receptor, endocytosis, and oxidative phosphorylation signaling pathways. Additionally, underlying lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA ceRNA networks were then constructed to further understand their interaction during S. Enteritidis infection. Lnc_012227 and novel_circ_0004892 were identified as ceRNAs, which could compete with miR-let-7g-5p and thereby indirectly modulating map3k8 expression to control S. Enteritidis infection. Together, our data thus identified promising candidate ncRNAs responsible for regulating S. Enteritidis infection in the preovulatory follicles of ducks, offering new insights regarding the ovarian transmission of this pathogen.

scholarly journals CircFAM114A2 Inhibits Bladder Cancer Proliferation and Promotes Cisplatin Sensitivity via the miR-222-3p/P27 and miR-146a-5p/P21 Cascades

2020 ◽  
Author(s):  
Jiancheng Lu ◽  
Zijian Zhou ◽  
Jingzi Wang ◽  
Xiao Yang ◽  
Hao Yu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Bladder Cancer ◽  
Nude Mice ◽  
Target Genes ◽  
Histological Grade ◽  
Tumor Formation ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Cancer Proliferation ◽  
Downstream Target

Abstract Background: Circular RNAs (circRNAs) are noncoding RNAs that have the structure of a covalently closed loop. Increasing data has proved that circRNA can influence the development and progression of tumors. CircFAM114A2 is generated from several exons of FAM114A2. However, the function and mechanisms of circFAM114A2 in bladder cancer (BCa) remain unclear. Methods: Here, to elucidate the potential roles of circFAM114A2 in BCa, we conducted RNA-sequencing on 5 pairs of BCa samples and screened for circRNAs. CircRNAs, microRNAs (miRNAs) and mRNAs, as well as levels of P27 and P21, in human cells and tissues were detected by qRT-PCR and western blot, respectively. CircRNA-miRNA interactions and miRNA-downstream mRNAs interactions were investigated by RNA pull-down assay and fluorescence in situ hybridization (FISH) or luciferase reporter assays, respectively. Then, the function of circFAM114A2 in BCa was explored using cell proliferation, cell cycle and tumorigenesis assays in nude mice. Finally, the function of circFAM114A2 in cisplatin chemo-sensitivity in BCa was detected by IC50 and tumor formation of xenograft in cisplatin-treated nude mice. Results: We discovered that circFAM114A2 levels were decreased in BCa cell lines and tissues. According to follow-up data, BCa patients with higher circFAM114A2 expression had better survival. Importantly, the levels of circFAM114A2 were associated with the histological grade of BCa. Overexpression of circFAM114A2 inhibited cell proliferation and increased sensitivity to cisplatin chemotherapy. Mechanistically, circFAM114A2 directly sponged miR-222-3p/miR-146a-5p and subsequently influenced the expression of the downstream target genes P27/P21, which, in turn, inhibited progression of BCa. Conclusion: In conclusion, circFAM114A2 acted as a tumor suppressor through a novel circFAM114A2/miR-222-3p/P27 and circFAM114A2/miR-146a-5p/P21 pathway. CircFAM1142 has therefore great potential as a prognostic biomarker and therapeutic target for BCa.

scholarly journals CircularLRRC7 is a Potential Tumor Suppressor Associated With miR-1281 and PDXP Expression in Glioblastoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Xue Kong ◽  
Ruiting Xu ◽  
Wei Wang ◽  
Minghui Zeng ◽  
Yuan Li ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Target Genes ◽  
Progression Free Survival ◽  
Bioinformatic Analysis ◽  
Circular Rnas ◽  
Normal Brain ◽  
Free Survival ◽  
Downstream Target ◽  
Intersection Analysis ◽  
Mirna Expression Data

Circular RNAs (circRNAs) are usually enriched in neural tissues, yet about 80% circRNAs have lower expression in gliomas relative to normal brains, highlighting the importance of circRNAs as tumor suppressors. However, the clinical impact as well as the pathways regulated by the tumor-suppressive circRNAs remain largely unknown in glioblastoma (GBM). Through bioinformatic analysis followed by experimental validation, we found that hsa_circ_0114014 (circLRRC7) was dramatically down-regulated in GBM when compared with normal brain tissues (p < 0.0001). GBM patients with a lower circLRRC7 expression had poorer progression-free survival (PFS, p < 0.05) and overall survival (OS, p < 0.05). Analyses of the predicted target miRNAs of circLRRC7 in CSCD and CRI databases, in combination with the miRNA expression data in GBMs and normal brains from GSE database, revealed miR-1281 as a potential downstream target of circLRRC7. Subsequently, the target genes of hsa-mir-1281 were predicted by TargetScan, miRDB and miRNATAR databases. Intersection analysis and correlation test indicated that PDXP was a potential target of miR-1281. In summary, circLRRC7 may be a tumor suppressor that associated with miR-1281 and PDXP expression in GBM, which may provide novel therapeutic targets for GBM treatment.

scholarly journals Emerging evidence on noncoding-RNA regulatory machinery in intervertebral disc degeneration: a narrative review

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Hao-Yu Guo ◽  
Ming-Ke Guo ◽  
Zhong-Yuan Wan ◽  
Fang Song ◽  
Hai-Qiang Wang
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Noncoding Rna ◽  
Regulatory Networks ◽  
Intervertebral Disc Degeneration ◽  
Target Genes ◽  
Noncoding Rnas ◽  
Circular Rnas ◽  
Form Complex ◽  
Underlying Mechanisms

AbstractIntervertebral disc degeneration (IDD) is the most common cause of low-back pain. Accumulating evidence indicates that the expression profiling of noncoding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long noncoding RNAs (lncRNAs), are different between intervertebral disc tissues obtained from healthy individuals and patients with IDD. However, the roles of ncRNAs in IDD are still unclear until now. In this review, we summarize the studies concerning ncRNA interactions and regulatory functions in IDD. Apoptosis, aberrant proliferation, extracellular matrix degradation, and inflammatory abnormality are tetrad fundamental pathologic phenotypes in IDD. We demonstrated that ncRNAs are playing vital roles in apoptosis, proliferation, ECM degeneration, and inflammation process of IDD. The ncRNAs participate in underlying mechanisms of IDD in different ways. MiRNAs downregulate target genes’ expression by directly binding to the 3′-untranslated region of mRNAs. CircRNAs and lncRNAs act as sponges or competing endogenous RNAs by competitively binding to miRNAs and regulating the expression of mRNAs. The lncRNAs, circRNAs, miRNAs, and mRNAs widely crosstalk and form complex regulatory networks in the degenerative processes. The current review presents novel insights into the pathogenesis of IDD and potentially sheds light on the therapeutics in the future.

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