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.

scholarly journals A circular RNAs dataset landscape reveals potential signatures for the detection and prognosis of early-stage lung adenocarcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhiying Chen ◽  
Jiahui Wei ◽  
Min Li ◽  
Yongjuan Zhao
Keyword(s):  
Functional Analysis ◽  
Survival Analysis ◽  
Lung Adenocarcinoma ◽  
Target Genes ◽  
Interaction Analysis ◽  
Early Stage ◽  
Gene Interaction ◽  
Gene Expression Omnibus ◽  
Circular Rnas ◽  
Cerna Network

Abstract Background This study aimed to identify potential circular ribonucleic acid (circRNA) signatures involved in the pathogenesis of early-stage lung adenocarcinoma (LAC). Methods The circRNA sequencing dataset of early-stage LAC was downloaded from the Gene Expression Omnibus database. First, the differentially expressed circRNAs (DEcircRNAs) between tumour and non-tumour tissues were screened. Then, the corresponding miRNAs and their target genes were predicted. In addition, prognosis-related genes were identified using survival analysis and further used to build a network of competitive endogenous RNAs (ceRNAs; DEcircRNA–miRNA–mRNA). Finally, the functional analysis and drug–gene interaction analysis of mRNAs in the ceRNA network was performed. Results A total of 35 DEcircRNAs (30 up-regulated and 5 down-regulated circRNAs) were identified. Moreover, 135 DEcircRNA–miRNA and 674 miRNA–mRNA pairs were predicted. The survival analysis of these target mRNAs revealed that 60 genes were significantly associated with survival outcomes in early-stage LAC. Of these, high levels of PSMA 5 and low levels of NAMPT, CPT 2 and TNFSF11 exhibited favourable prognoses. In addition, the DEcircRNA–miRNA–mRNA network was constructed, containing 5 miRNA–circRNA (hsa_circ_0092283/hsa-miR-762/hsa-miR-4685-5p; hsa_circ_0070610/hsa-let-7a-2-3p/hsa-miR-3622a-3p; hsa_circ_0062682/hsa-miR-4268) and 60 miRNA–mRNA pairs. Functional analysis of the genes in the ceRNA network showed that they were primarily enriched in the Wnt signalling pathway. Moreover, PSMA 5, NAMPT, CPT 2 and TNFSF11 had strong correlations with different drugs. Conclusion Three circRNAs (hsa_circ_0062682, hsa_circ_0092283 and hsa_circ_0070610) might be potential novel targets for the diagnosis of early-stage LAC.

scholarly journals Systematic Elucidation of the Potential Mechanisms of Core Chinese Materia Medicas in Treating Liver Cancer Based on Network Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Zhulin Wu ◽  
Lina Yang ◽  
Li He ◽  
Lianan Wang ◽  
Lisheng Peng
Keyword(s):  
Data Mining ◽  
Liver Cancer ◽  
Signaling Pathways ◽  
Target Genes ◽  
Primary Liver Cancer ◽  
Network Pharmacology ◽  
Data Mining Technique ◽  
Antitumor Effects ◽  
Bioactive Ingredients ◽  
Common Target

Objective. In this study, the data mining method was used to screen the core Chinese materia medicas (CCMMs) against primary liver cancer (PLC), and the potential mechanisms of CCMMs in treating PLC were analyzed based on network pharmacology. Methods. Traditional Chinese medicine (TCM) prescriptions for treating PLC were obtained from a famous TCM doctor in Shenzhen, China. According to the data mining technique, the TCM Inheritance Support System (TCMISS) was applied to excavate the CCMMs in the prescriptions. Then, bioactive ingredients and corresponding targets of CCMMs were collected using three different TCM online databases, and target genes of PLC were obtained from GeneCards and OMIM. Afterwards, common targets of CCMMs and PLC were screened. Furthermore, a network of CCMMs bioactive ingredients and common target gene was constructed by Cytoscape 3.7.1, and gene ontology (GO) and signaling pathways analyses were performed to explain the mechanism of CCMMs in treating PLC. Besides, protein-protein interaction (PPI) analysis was used to identify key target genes of CCMMs, and the prognostic value of key target genes was verified using survival analysis. Results. A total of 15 high-frequency Chinese materia medica combinations were found, and CCMMs (including Paeoniae Radix Alba, Radix Bupleuri, Macrocephalae Rhizoma, Coicis Semen, Poria, and Curcumae Radix) were identified by TCMISS. A total of 40 bioactive ingredients (e.g., quercetin, kaempferol, and naringenin) of CCMMs were obtained, and 202 common target genes of CCMMs and PLC were screened. GO analysis indicated that biological processes of CCMMs were mainly involved in response to drug, response to ethanol, etc. Pathway analysis demonstrated that CCMMs exerted its antitumor effects by acting on multiple signaling pathways, including PI3K-Akt, TNF, and MAPK pathways. Also, some key target genes of CCMMs were determined by PPI analysis, and four genes (MAPK3, VEGFA, EGF, and EGFR) were found to be correlated with survival in PLC patients. Conclusion. Based on data mining and network pharmacology methods, our results showed that the therapeutic effect of CCMMs on PLC may be realized by acting on multitargets and multipathways related to the occurrence and development of PLC.

scholarly journals Alcohol Promotes Hepatocellular Carcinoma Metastasis Through SIRT7-Dependent EMT Regulation

2021 ◽  
Author(s):  
Chen Zhang ◽  
Jinqiu Zhao ◽  
Jie Zhao ◽  
Bohao Liu ◽  
Wenbin Tang ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cancer Metastasis ◽  
Disease Free Survival ◽  
Critical Factor ◽  
Bioinformatic Analysis ◽  
Disease Stage ◽  
Qrt Pcr ◽  
E Cadherin

Abstract Background Long-term alcohol use is a confirmed risk factor of liver cancer tumorigenesis and metastasis. Multiple mechanisms responsible for alcohol related tumorigenesis have been proposed, including toxic reactive metabolite production, oxidative stress and fat accumulation which trigger hepatocyte cell death and inflammation. However, mechanisms underlying alcohol-mediated liver cancer metastasis remain largely unknown. Methods SIRT7 expression pattern and its association with HCC metastasis were investigated by bioinformatic analysis and verified by western blot and immunochemistry in HCC tissues. The biological consequences of overexpression and knockdown of SIRT7 in HCC metastasis were studied in vitro and in vivo. qRT-PCR, immunofluorescence assay, ChIP assay were utilized to assess the effects of SIRT7 on E-cadherin expression. Effects of alcohol on SIRT7 expression were evaluated by qRT-PCR, immunofluorescence and inhibitor treatments and pulmonary metastasis model mice fed with Lieber Decarli alcohol diet were used to clarify the mechanisms by which SIRT7 facilitated alcohol mediated HCC metastasis. Results SIRT7 is a critical factor in promoting liver cancer metastasis. SIRT7 expression is closely associated with disease stage and high SIRT7 predicts worse overall and disease-free survival. Overexpression of SIRT7 promotes HCC cell migration and EMT while knockdown of SIRT7 showed opposite effects. Mechanistically, we found that SIRT7 suppresses E-Cadherin expression through promoter binding and H3K18 deacetylation. Most importantly, we identified that alcohol upregulates SIRT7 expression in hepatocyte both in vitro and in vivo. Reducing SIRT7 activity completely abolished alcohol-mediated liver cancer metastasis in vivo. Conclusion SIRT7-dependent EMT regulation is a pivotal regulatory mechanism of alcohol-mediated HCC metastasis and reveals previously unidentified roles of SIRT7 in promoting EMT and metastasis in human HCC. Therapeutic strategies that inhibit SIRT7 may offer novel options for the treatment of HCC.

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.

Data Mining for Drug Repurposing and New Targets Identification for Radioprotection

2017 ◽  
Vol 2 (3) ◽  
pp. 343 ◽  
Author(s):  
Yogesh Kumar Verma ◽  
Gurudutta Gangenahalli
Keyword(s):  
Data Mining ◽  
Target Genes ◽  
Tissue Injury ◽  
Drug Repurposing ◽  
Gene Interaction ◽  
Pharmacological Agents ◽  
New Targets ◽  
Cancer Pathways ◽  
Interaction Database ◽  
Us Fda

<p>Ionising radiation (IR) is responsible for various types of tissue injury leading to morbidity at low doses and mortality at high radiation exposure. Although many radioprotective and pharmacological agents are being tested for decreasing radiation injury, however, the availability of Amifostine as the only clinically used radioprotector with limited indication has prompted us to find out new potential molecules through drugs repurposing for protecting or decreasing radiation damage by data mining. In this work we have used text-mining based network generation approach to find out the gene targets of radioprotectors under evaluation by Agilent Literature Search app in Cytoscape. Extracted genes were evaluated for their association with radiation in Radiation Genes database. These genes were searched against therapeutic drugs and molecules under clinical trial in the Drug Gene Interaction database. We found that most of the radiation target genes were involved in cell death, proliferation, homeostasis, cell cycle and cancer pathways. Many of these genes were druggable and could be targeted by the drugs under clinical research, whereas there were few genes (new targets), which were never considered for radioprotective drug development. This study would likely help in repurposing of identified drugs for use in the event of radiation fallout, keeping in mind that no radiation medical countermeasure for acute radiation syndrome has been approved by the US FDA for use in humans. Results also revealed new target genes for drug targeting and indicates use of similar pipeline in other pathologies for drug repurposing and development.<br /><br /></p>

283 PREDICTION OF miRNA TARGET GENES INVOLVED IN LIVER CANCER PATHWAYS AND ITS VALIDATION

2013 ◽  
Vol 58 ◽  
pp. S120 ◽  
Author(s):  
M. Amer ◽  
E. El-Ahwany ◽  
M. Elhefnawi ◽  
A.F. Awad ◽  
N. Abdel Gawad ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Mirna Target ◽  
Target Genes ◽  
Cancer Pathways

scholarly journals Sex-Biased lncRNA Signature in Fetal Growth Restriction (FGR)

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 921
Author(s):  
Aleksandra Lipka ◽  
Jan Pawel Jastrzebski ◽  
Lukasz Paukszto ◽  
Karol Gustaw Makowczenko ◽  
Elzbieta Lopienska-Biernat ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Target Genes ◽  
Active Regions ◽  
Bioinformatic Analysis ◽  
Growth Restriction ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Differential Analysis ◽  
Protein Coding

Impaired fetal growth is one of the most important causes of prematurity, stillbirth and infant mortality. The pathogenesis of idiopathic fetal growth restriction (FGR) is poorly understood but is thought to be multifactorial and comprise a range of genetic causes. This research aimed to investigate non-coding RNAs (lncRNAs) in the placentas of male and female fetuses affected by FGR. RNA-Seq data were analyzed to detect lncRNAs, their potential target genes and circular RNAs (circRNAs); a differential analysis was also performed. The multilevel bioinformatic analysis enabled the detection of 23,137 placental lncRNAs and 4263 of them were classified as novel. In FGR-affected female fetuses’ placentas (ff-FGR), among 19 transcriptionally active regions (TARs), five differentially expressed lncRNAs (DELs) and 12 differentially expressed protein-coding genes (DEGs) were identified. Within 232 differentially expressed TARs identified in male fetuses (mf-FGR), 33 encompassed novel and 176 known lncRNAs, and 52 DEGs were upregulated, while 180 revealed decreased expression. In ff-FGR ACTA2-AS1, lncRNA expression was significantly correlated with five DEGs, and in mf-FGR, 25 TARs were associated with DELs correlated with 157 unique DEGs. Backsplicing circRNA processes were detected in the range of H19 lncRNA, in both ff- and mf-FGR placentas. The performed global lncRNAs characteristics in terms of fetal sex showed dysregulation of DELs, DEGs and circRNAs that may affect fetus growth and pregnancy outcomes. In female placentas, DELs and DEGs were associated mainly with the vasculature, while in male placentas, disturbed expression predominantly affected immune processes.

scholarly journals Regulatory Network Analysis in Estradiol-Treated Human Endothelial Cells

2021 ◽  
Vol 22 (15) ◽  
pp. 8193
Author(s):  
Daniel Pérez-Cremades ◽  
Ana B. Paes ◽  
Xavier Vidal-Gómez ◽  
Ana Mompeón ◽  
Carlos Hermenegildo ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Regulatory Network ◽  
Mirna Target ◽  
Target Genes ◽  
Functional Characterization ◽  
Human Endothelial Cells ◽  
Mrna Targets ◽  
Canonical Pathways

Background/Aims: Estrogen has been reported to have beneficial effects on vascular biology through direct actions on endothelium. Together with transcription factors, miRNAs are the major drivers of gene expression and signaling networks. The objective of this study was to identify a comprehensive regulatory network (miRNA-transcription factor-downstream genes) that controls the transcriptomic changes observed in endothelial cells exposed to estradiol. Methods: miRNA/mRNA interactions were assembled using our previous microarray data of human umbilical vein endothelial cells (HUVEC) treated with 17β-estradiol (E2) (1 nmol/L, 24 h). miRNA–mRNA pairings and their associated canonical pathways were determined using Ingenuity Pathway Analysis software. Transcription factors were identified among the miRNA-regulated genes. Transcription factor downstream target genes were predicted by consensus transcription factor binding sites in the promoter region of E2-regulated genes by using JASPAR and TRANSFAC tools in Enrichr software. Results: miRNA–target pairings were filtered by using differentially expressed miRNAs and mRNAs characterized by a regulatory relationship according to miRNA target prediction databases. The analysis identified 588 miRNA–target interactions between 102 miRNAs and 588 targets. Specifically, 63 upregulated miRNAs interacted with 295 downregulated targets, while 39 downregulated miRNAs were paired with 293 upregulated mRNA targets. Functional characterization of miRNA/mRNA association analysis highlighted hypoxia signaling, integrin, ephrin receptor signaling and regulation of actin-based motility by Rho among the canonical pathways regulated by E2 in HUVEC. Transcription factors and downstream genes analysis revealed eight networks, including those mediated by JUN and REPIN1, which are associated with cadherin binding and cell adhesion molecule binding pathways. Conclusion: This study identifies regulatory networks obtained by integrative microarray analysis and provides additional insights into the way estradiol could regulate endothelial function in human endothelial cells.

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