Abstract WMP41: Characterization of MicroRNAs and Their Target Proteins in Distal Axons of Cortical Neurons

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Chao Li ◽  
Yi Zhang ◽  
Albert M Levin ◽  
Michael Chopp ◽  
Zheng Gang Zhang
Keyword(s):  
Cortical Neurons ◽  
Mirna Target ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Axonal Growth ◽  
Bioinformatic Analysis ◽  
Inhibitory Effect ◽  
Bioinformatic Tools ◽  
Molecular Information

Introduction: Axonal growth is essential for the establishment of a functional neuronal network. Molecular information of axon is limited. MicroRNAs (miRNAs) regulate post-transcriptional gene expression. We hypothesized that axonal miRNAs are locally relevant to their target genes. Methods: Proteins and RNAs were extracted from distal axons of cortical neurons cultured in a microfluidic device. A mass spectrometer and miRNA arrays were used to measure proteins and miRNAs, respectively. Ingenuity Pathway Analysis (IPA) and Database for Annotation, Visualization and Integrated Discovery (DAVID) bioinformatic tools were used to make in silico predictions of functionally relevant miRNA target genes. Results: Proteomic showed that distal axons contained 883 proteins. Bioinformatic analysis showed the presence of 94 proteins that regulate axonal growth. To identify relevant miRNAs to these 94 proteins, miRNAs with 8mer sites that exactly match target genes were considered, based on the fact that 8mer sites efficaciously affect miRNA-target interactions. Of the 94 genes, we found that there were 56 candidate genes that can be targeted by 62 miRNAs enriched in axons. Among them, we validated 13 proteins and 11 miRNAs, respectively, by means of Western blot and RT-PCR. To examine target genes, we treated axons with chondroitin sulfate proteoglycans (CSPGs) that inhibit axonal growth and examined alterations of these proteins and miRNAs in the distal axons. We found that elevation of miR-203a, -133b, -29abc and -92ab were associated with reduced AKT, MTOR, PI3Kp85, DPYSL2, MAP1B, PPP2CA and DCX proteins, whereas decreased miR-15b, -26b, -34b, -376b, -128, -381 and -195 were accompanied by increased proteins of EZR, KIF5A, RTN4, GSK3B, and ROCK2. Bioinformatic analysis revealed that these miRNAs and proteins are highly related to the axonal growth network. These data suggest that miRNAs altered by CSPGs functionally target these genes for mediating the inhibitory effect of CSPGs on axonal growth. Conclusions: Our bioinformatic analyses of miRNAs and proteins in the distal axon identifies an interconnected group of miRNAs and their target genes that regulate axonal growth, which provides new insight into the molecular mechanisms underlying axonal growth.

Elevation of MicroRNA-126 Levels in Intracranial Aneurysm and Bioinformatic Analysis of Potential Molecular Mechanisms

2021 ◽  
Vol 11 (4) ◽  
pp. 573-579
Author(s):  
Pan Huang ◽  
Min Xu ◽  
Xiao-Ying He
Keyword(s):  
Intracranial Aneurysm ◽  
Peripheral Blood ◽  
Target Gene ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Kegg Pathway ◽  
Bioinformatic Analysis ◽  
Control Group ◽  
Potential Target ◽  
Fas Signaling

The study is to investigation of microRNA-126 levels in patients with intracranial aneurysm and bioinformatic analysis of the molecular mechanisms involved. A total of 166 patients with ICA who were hospitalized or examined in our hospital from September 2015 to December 2017 were used as the experimental group (ICA group). This group included 120 patients with unruptured intracranial aneurysm (UICA; UICA group) and 46 patients with ruptured intracranial aneurysm (RICA); RICA group). The UICA group was further subdivided into 42 surgical groups (S group) and 78 nonsurgical groups (NS group). Sixty-three normal people without intracranial aneurysms were selected as the control group. RT-PCR was used to quantitatively detect the relative expression of microRNA- 126 in peripheral blood mononuclear cells at the time of admission and immediately after surgery. The UCSC database was used to analyze the gene locus and homology of microRNA-126. The TargetScan database and CoMeTa database were used to predict the potential target genes of microRNA-126. The DAVID database was used to enrich the function of potential target genes of microRNA-126 (GO enrichment) and KEGG pathway enrichment for analysis. The expression level of microRNA-126 in peripheral blood was significantly higher in the ICA group than in the control group (P <0.01), significantly higher in the RICA group than in the UICA group (P <0.05). Expression was also higher in the NS group than in the S group but the difference was nonsignificant (P >0.05). A total of 15 potential target genes including ITGA6, CRK, PCDH7, and ADAM9 were identified through the target gene prediction software and GO analysis and KEGG pathway analysis showed that the function of the microRNA-126 target gene was mainly focused on protein binding and the FAS signaling pathway. In Conclusion the microRNA-126 is up-regulated in ICA patients and affects ICA by regulating multiple target genes in the FAS signaling pathway.

scholarly journals Characteristic Analysis from Excessive to Deficient Syndromes in Hepatocarcinoma Underlying miRNA Array Data

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Qi-Long Chen ◽  
Yi-Yu Lu ◽  
Gui-Biao Zhang ◽  
Ya-Nan Song ◽  
Qian-Mei Zhou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mirna Target ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Hierarchical Cluster ◽  
Characteristic Analysis ◽  
Array Data ◽  
Mirna Array ◽  
Differentially Expressed Mirnas ◽  
Similar Complex

Traditional Chinese medicine (TCM) treatment is regarded as a safe and effective method for many diseases. In this study, the characteristics among excessive, excessive-deficient, and deficient syndromes of Hepatocellular carcinoma (HCC) were studied using miRNA array data. We first calculated the differentially expressed miRNAs based on random modulet-test and classified three TCM syndromes of HCC using SVM method. Then, the weighted miRNA-target networks were constructed for different TCM syndromes using predicted miRNA targets. Subsequently, the prioritized target genes of upexpression network of TCM syndromes were analyzed using DAVID online analysis. The results showed that there are distinctly different hierarchical cluster and network structure of TCM syndromes in HCC, but the excessive-deficient combination syndrome is extrinsically close to deficient syndrome. GO and pathway analysis revealed that the molecular mechanisms of excessive-deficient and deficient syndromes of HCC are more complex than excessive syndrome. Furthermore, although excessive-deficient and deficient syndromes have similar complex mechanisms, excessive-deficient syndrome is more involved than deficient syndrome in development of cancer process. This study suggested that miRNAs might be important mediators involved in the changing process from excessive to deficient syndromes and could be potential molecular markers for the diagnosis of TCM syndromes in HCC.

scholarly journals Genome-wide investigation of microRNAs and expression profiles during rhizome development in ginger (Zingiber officinale Roscoe)

BMC Genomics ◽  
2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Haitao Xing ◽  
Yuan Li ◽  
Yun Ren ◽  
Ying Zhao ◽  
Xiaoli Wu ◽  
...  
Keyword(s):  
Mirna Target ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Qrt Pcr ◽  
Putative Target ◽  
Genome Wide ◽  
Ginger Rhizome ◽  
Rhizome Development

Abstract Background MicroRNAs (miRNAs) are endogenous, non-coding small functional RNAs that govern the post-transcriptional regulatory system of gene expression and control the growth and development of plants. Ginger is an herb that is well-known for its flavor and medicinal properties. The genes involved in ginger rhizome development and secondary metabolism have been discovered, but the genome-wide identification of miRNAs and their overall expression profiles and targets during ginger rhizome development are largely unknown. In this study, we used BGISEQ-500 technology to perform genome-wide identification of miRNAs from the leaf, stem, root, flower, and rhizome of ginger during three development stages. Results In total, 104 novel miRNAs and 160 conserved miRNAs in 28 miRNA families were identified. A total of 181 putative target genes for novel miRNAs and 2772 putative target genes for conserved miRNAs were predicted. Transcriptional factors were the most abundant target genes of miRNAs, and 17, 9, 8, 4, 13, 8, 3 conserved miRNAs and 5, 7, 4, 5, 5, 15, 9 novel miRNAs showed significant tissue-specific expression patterns in leaf, stem, root, flower, and rhizome. Additionally, 53 miRNAs were regarded as rhizome development-associated miRNAs, which mostly participate in metabolism, signal transduction, transport, and catabolism, suggesting that these miRNAs and their target genes play important roles in the rhizome development of ginger. Twelve candidate miRNA target genes were selected, and then, their credibility was confirmed using qRT-PCR. As the result of qRT-PCR analysis, the expression of 12 candidate target genes showed an opposite pattern after comparison with their miRNAs. The rhizome development system of ginger was observed to be governed by miR156, miR319, miR171a_2, miR164, and miR529, which modulated the expression of the SPL, MYB, GRF, SCL, and NAC genes, respectively. Conclusion This is a deep genome-wide investigation of miRNA and identification of miRNAs involved in rhizome development in ginger. We identified 52 rhizome-related miRNAs and 392 target genes, and this provides an important basis for understanding the molecular mechanisms of the miRNA target genes that mediate rhizome development in ginger.

scholarly journals Genome-wide identification and characterization of long non-coding RNAs conferring resistance to Colletotrichum gloeosporioides in walnut (Juglans regia)

2020 ◽  
Author(s):  
Shan Feng ◽  
Hongcheng Fang ◽  
Xia Liu ◽  
Yuhui Dong ◽  
Qingpeng Wang ◽  
...  
Keyword(s):  
Disease Resistance ◽  
Plant Disease Resistance ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Colletotrichum Gloeosporioides ◽  
Juglans Regia ◽  
Bioinformatic Analysis ◽  
Genome Wide ◽  
Phenylpropanoid Biosynthesis ◽  
Non Coding Rnas

Abstract Background: Walnut anthracnose caused by Colletotrichum gloeosporioides (Penz.) Penz. and Sacc. is an important walnut production problem in China. Although the long non-coding RNAs (lncRNAs) are important for plant disease resistance , the molecular mechanisms underlying resistance to C. gloeosporioides in walnut remain poorly understood.Results: The anthracnose-resistant F26 fruits from the B26 clone and the anthracnose-susceptible F423 fruits from the 4-23 clone of walnut were used as the test materials. Specifically, we performed a comparative transcriptome analysis of F26 and F423 fruit bracts to identify differentially expressed LncRNAs (DELs) at five time-points (tissues at 0 hpi, pathological tissues at 24 hpi, 48 hpi, 72 hpi, and distal uninoculated tissues at 120 hpi). Compared with F423, a total of 14525 DELs were identified, including 10645 upregulated lncRNAs and 3846 downregulated lncRNAs in F26. The number of upregulated lncRNAs in F26 compared to in F423 was significantly higher at the early stages of C. gloeosporioides infection. A total of 5 modules related to disease resistance were screened by WGCNA and the target genes of lncRNAs were obtained. Bioinformatic analysis showed that the target genes of upregulated lncRNAs were enriched in immune-related processes during the infection of C. gloeosporioides, such as activation of innate immune response, defense response to bacterium, incompatible interaction and immune system process, and enriched in plant hormone signal transduction, phenylpropanoid biosynthesis and other pathways. And 124 known target genes for 96 hub lncRNAs were predicted, including 10 known resistance genes. The expression of 5 lncRNAs and 5 target genes was confirmed by qPCR, which was consistent with the RNA-seq data.Conclusions: The results of this study provide the basis for future functional characterizations of lncRNAs regarding the C. gloeosporioides resistance of walnut fruit bracts.

scholarly journals Identification and validation of key miRNAs and miRNA–mRNA regulatory network associated with uterine involution in postpartum Kazakh sheep

2021 ◽  
Vol 64 (1) ◽  
pp. 119-129
Author(s):  
Heng Yang ◽  
Lin Fu ◽  
Qifeng Luo ◽  
Licai Li ◽  
Fangling Zheng ◽  
...  
Keyword(s):  
Mirna Target ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Gene Prediction ◽  
Biological Effects ◽  
Differentially Expressed ◽  
Illumina Hiseq ◽  
Go Annotation ◽  
Uterine Involution ◽  
Differentially Expressed Mirnas

Abstract. MicroRNAs (miRNAs) are widely expressed in different mammalian tissues and exert their biological effects through corresponding target genes. miRNA target genes can be rapidly and efficiently identified and screened by combining bioinformatics prediction and experimental validation. To investigate the possible molecular regulatory mechanisms involving miRNAs during uterine involution in postpartum ewes, we used Illumina HiSeq sequencing technology to screen for the number and characteristics of miRNAs in faster uterine involution and normal uterine involution group. A total of 118 differentially expressed miRNAs, including 33 known miRNAs and 85 new miRNAs, were identified in the hypothalamic library, whereas 54 miRNAs, including 5 known miRNAs and 49 new miRNAs, were identified in the uterine library. Screening with four types of gene prediction software revealed 73 target genes associated with uterine involution, and subsequently, GO annotation and KEGG pathway analysis were performed. The results showed that, in the hypothalamic–uterine axis, uterine involution in postpartum ewes might primarily involve two miRNA-target gene pairs, namely, miRNA-200a–PTEN and miRNA-133–FGFR1, which can participate in GnRH signal transduction in the upstream hypothalamus and in the remodeling process at the downstream uterus, through the PI3K–AKT signaling pathway to influence the recovery of the morphology and functions of the uterus during the postpartum period in sheep. Therefore, identification of differentially expressed miRNAs in this study fills a gap in the research related to miRNAs in uterine involution in postpartum ewes and provides an important reference point for a comprehensive understanding of the molecular mechanisms underlying the regulation of postpartum uterine involution in female livestock.

scholarly journals Ischemic Cerebral Endothelial Cell–Derived Exosomes Promote Axonal Growth

Stroke ◽  
2020 ◽  
Vol 51 (12) ◽  
pp. 3701-3712
Author(s):  
Yi Zhang ◽  
Yi Qin ◽  
Michael Chopp ◽  
Chao Li ◽  
Amy Kemper ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Neuronal Cell ◽  
Axonal Growth ◽  
Mature Mirnas ◽  
Bioinformatic Analysis ◽  
Axonal Outgrowth ◽  
Ischemic Brain ◽  
Neuronal Homeostasis ◽  
Neuronal Cell Bodies

Background and Purpose: Cerebral endothelial cells (CECs) and axons of neurons interact to maintain vascular and neuronal homeostasis and axonal remodeling in normal and ischemic brain, respectively. However, the role of exosomes in the interaction of CECs and axons in brain under normal conditions and after stroke is unknown. Methods: Exosomes were isolated from CECs of nonischemic rats and is chemic rats (nCEC-exos and isCEC-exos), respectively. A multicompartmental cell culture system was used to separate axons from neuronal cell bodies. Results: Axonal application of nCEC-exos promotes axonal growth of cortical neurons, whereas isCEC-exos further enhance axonal growth than nCEC-exos. Ultrastructural analysis revealed that CEC-exos applied into distal axons were internalized by axons and reached to their parent somata. Bioinformatic analysis revealed that both nCEC-exos and isCEC-exos contain abundant mature miRNAs; however, isCEC-exos exhibit more robust elevation of select miRNAs than nCEC-exos. Mechanistically, axonal application of nCEC-exos and isCEC-exos significantly elevated miRNAs and reduced proteins in distal axons and their parent somata that are involved in inhibiting axonal outgrowth. Blockage of axonal transport suppressed isCEC-exo–altered miRNAs and proteins in somata but not in distal axons. Conclusions: nCEC-exos and isCEC-exos facilitate axonal growth by altering miRNAs and their target protein profiles in recipient neurons.

The Use of Chemical Compounds to Identify the Regulatory Mechanisms of Vertebrate Circadian Clocks

2020 ◽  
Vol 21 (5) ◽  
pp. 425-432
Author(s):  
Yoshimi Okamoto-Uchida ◽  
Akari Nishimura ◽  
Junko Izawa ◽  
Atsuhiko Hattori ◽  
Nobuo Suzuki ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Chemical Compounds ◽  
Stability Control ◽  
Circadian Clocks ◽  
Light Signaling ◽  
Negative Feedback Loops ◽  
Exact Timing

Circadian clocks are intrinsic, time-tracking processes that confer a survival advantage on an organism. Under natural conditions, they follow approximately a 24-h day, modulated by environmental time cues, such as light, to maximize an organism’s physiological efficiency. The exact timing of this rhythm is established by cell-autonomous oscillators called cellular clocks, which are controlled by transcription–translation negative feedback loops. Studies of cell-based systems and wholeanimal models have utilized a pharmacological approach in which chemical compounds are used to identify molecular mechanisms capable of establishing and maintaining cellular clocks, such as posttranslational modifications of cellular clock regulators, chromatin remodeling of cellular clock target genes’ promoters, and stability control of cellular clock components. In addition, studies with chemical compounds have contributed to the characterization of light-signaling pathways and their impact on the cellular clock. Here, the use of chemical compounds to study the molecular, cellular, and behavioral aspects of the vertebrate circadian clock system is described.

Discovery of Biomarkers in Hepatocellular Carcinoma Metastasis Using Bioinformatic Analysis

2020 ◽  
Vol 15 ◽  
Author(s):  
Jinrui Wei ◽  
Haroon ur Rashid ◽  
Lichuan Wu
Keyword(s):  
Data Mining ◽  
Liver Cancer ◽  
Mirna Target ◽  
Cancer Metastasis ◽  
Target Genes ◽  
Interaction Analysis ◽  
Gene Interaction ◽  
Bioinformatic Analysis ◽  
Mirna Microarray ◽  
Carcinoma Metastasis

Background: Liver cancer is one of the most deadly malignancies worldwide. Tumor metastasis is the main cause of liver cancer related death. So far the mechanism of liver cancer metastasis are far away from fully elucidated. In this study, we aim to discover key regulators involved in liver cancer metastasis by data mining. Methods: Two different types of data including mRNA microarray (GSE6222 and GSE6764) and miRNA microarray (GSE67138) were analyzed. A total of 83 intersectant differently expressed genes (DEGs) with same expression pattern in GSE6222 and GSE6764 were identified. One hundred and thirty one differently expressed miRNAs (DEMs) were identified in GSE 67138. Further, a total of 26 pairs of miRNAtarget including 18 DEMs and 13 DEGs were identified as critical miRNA-target axis via miRNA-target gene interaction analysis. Result and Conclusion: Among the 18 DEMs and 13 DEGs, 10 miRNAs and 10 target genes are significantly correlated with patients’ survival (p < 0.05). Our results and methods might be interesting for data mining and helpful for further experimental functional validation.

Sequencing and characterization of lncRNAs in the breast muscle of Gushi and Arbor Acres chickens

Genome ◽  
2018 ◽  
Vol 61 (5) ◽  
pp. 337-347 ◽  
Author(s):  
Tuanhui Ren ◽  
Zhuanjian Li ◽  
Yu Zhou ◽  
Xuelian Liu ◽  
Ruili Han ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Muscle Development ◽  
Target Genes ◽  
Expression Profiles ◽  
Economic Value ◽  
Muscle Quality ◽  
Specific Expression ◽  
Chicken Muscle ◽  
Molecular Regulatory Mechanisms

Chicken muscle quality is one of the most important factors determining the economic value of poultry, and muscle development and growth are affected by genetics, environment, and nutrition. However, little is known about the molecular regulatory mechanisms of long non-coding RNAs (lncRNAs) in chicken skeletal muscle development. Our study aimed to better understand muscle development in chickens and thereby improve meat quality. In this study, Ribo-Zero RNA-Seq was used to investigate differences in the expression profiles of muscle development related genes and associated pathways between Gushi (GS) and Arbor Acres (AA) chickens. We identified two muscle tissue specific expression lncRNAs. In addition, the target genes of these lncRNAs were significantly enriched in certain biological processes and molecular functions, as demonstrated by Gene Ontology (GO) analysis, and these target genes participate in five signaling pathway, as revealed by an analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Taken together, these data suggest that different lncRNAs might be involved in regulating chicken muscle development and growth and provide new insight into the molecular mechanisms of lncRNAs.

scholarly journals Genome-wide identification and characterization of long non-coding RNAs conferring resistance to Colletotrichum gloeosporioides in walnut (Juglans regia)

2020 ◽  
Author(s):  
Shan Feng ◽  
Hongcheng Fang ◽  
Xia Liu ◽  
Yuhui Dong ◽  
Qingpeng Wang ◽  
...  
Keyword(s):  
Disease Resistance ◽  
Plant Disease Resistance ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Colletotrichum Gloeosporioides ◽  
Juglans Regia ◽  
Bioinformatic Analysis ◽  
Genome Wide ◽  
Phenylpropanoid Biosynthesis ◽  
Non Coding Rnas

Abstract Background: Walnut anthracnose caused by Colletotrichum gloeosporioides (Penz.) Penz. and Sacc. is an important walnut production problem in China. Although the long non-coding RNAs (lncRNAs) are important for plant disease resistance , the molecular mechanisms underlying resistance to C. gloeosporioides in walnut remain poorly understood.Results: The anthracnose-resistant F26 fruits from the B26 clone and the anthracnose-susceptible F423 fruits from the 4-23 clone of walnut were used as the test materials. Specifically, we performed a comparative transcriptome analysis of F26 and F423 fruit bracts to identify differentially expressed LncRNAs (DELs) at five time-points (tissues at 0 hpi, pathological tissues at 24 hpi, 48 hpi, 72 hpi, and distal uninoculated tissues at 120 hpi). Compared with F423, a total of 14525 DELs were identified, including 10645 upregulated lncRNAs and 3846 downregulated lncRNAs in F26. The number of upregulated lncRNAs in F26 compared to in F423 was significantly higher at the early stages of C. gloeosporioides infection. A total of 5 modules related to disease resistance were screened by WGCNA and the target genes of lncRNAs were obtained. Bioinformatic analysis showed that the target genes of upregulated lncRNAs were enriched in immune-related processes during the infection of C. gloeosporioides, such as activation of innate immune response, defense response to bacterium, incompatible interaction and immune system process, and enriched in plant hormone signal transduction, phenylpropanoid biosynthesis and other pathways. And 124 known target genes for 96 hub lncRNAs were predicted, including 10 known resistance genes. The expression of 5 lncRNAs and 5 target genes was confirmed by qPCR, which was consistent with the RNA-seq data.Conclusions: The results of this study provide the basis for future functional characterizations of lncRNAs regarding the C. gloeosporioides resistance of walnut fruit bracts.

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