MicroRNA Expression Profiles Identify Biomarker for Differentiating the Embolic Stroke from Thrombotic Stroke

In order to identify potential biomarkers that distinguish the embolic stroke (ES) from thrombotic stroke (TS), a profile of microRNA expression was analyzed. The GSE60319 expression profile was downloaded from the Gene Expression Omnibus (GEO) database. The GEO2R was applied to screen for differentially expressed microRNAs (DEmiRNAs) between the embolic stroke group and thrombotic stroke group. The miRWalk was utilized to predict the target genes of DEmiRNAs. Genes associated with embolic stroke were downloaded from the Comparative Toxicogenomics Database. Cross reference of target genes to disease related genes was conducted to construct the DEmiRNA-gene network. The protein-protein interaction (PPI) network of overlapping genes was evaluated by STRING, using the MCODE and CytoHubba plugin of Cytoscape to identify the modules and hub genes. The enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG) in modules was performed. There were 30 microRNAs in total identified as DEmiRNAs between embolic stroke and thrombotic stroke groups, of which 8 were upregulated and 22 were downregulated. Among these differentially expressed miRNAs, miR-15a-5p, miR-17-5p, miR-19b-3p, and miR-20a-5p were significantly associated with an ES to TS. Using the miRWalk 3.0 online tool, target genes regulated by DEmiRNAs were predicted. In addition, disease related genes were predicted and compared with target genes of DEmiRNAs. 166 overlapped genes regulated by miR-15a-5p, miR-17-5p, miR-19b-3p, and miR-20a-5p were identified, suggesting their association with diseases that contributed to ES, mainly including atrial fibrillation, mitral valve stenosis, myocardial infarction, and aortic dissection. Therefore, miR-15a-5p, miR-17-5p, miR-19b-3p, and miR-20a-5p were promising candidate biomarkers for differentiating an ES from TS. The PPI network demonstrated that miR-15a-5p, miR-17-5p, miR-19b-3p, and miR-20a-5p were associated with an ES by mainly regulating “CCND1, E2F2, E2F3, ITCH, UBE4A, UBE3C, RBL2, FBXO31, EIF2C4, and EIF2C1”. Furthermore, miR-15a-5p and miR-17-5p may function through “cell cycle, prostate cancer, and small cell lung cancer” while miR-19b-3p and miR-20a-5p function through “insulin resistance, hepatitis B, and viral carcinogenesis” and “vasopressin-regulated water reabsorption”, respectively. However, these results were approached in the manner of bioinformatics analysis; therefore, further verification is required.

Download Full-text

Comprehensive bioinformatics analysis of mRNA expression profiles and identification of a miRNA–mRNA network associated with lupus nephritis

Lupus ◽

10.1177/0961203320925155 ◽

2020 ◽

Vol 29 (8) ◽

pp. 854-861

Author(s):

Jianbo Song ◽

Liqin Zhao ◽

Yuanping Li

Keyword(s):

Lupus Nephritis ◽

Mrna Expression ◽

Lupus Erythematosus ◽

Target Genes ◽

Expression Profiles ◽

Enrichment Analysis ◽

Gene Expression Omnibus ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Ppi Network

Objective Lupus nephritis (LN) is one of the serious complications of systemic lupus erythematosus. The aim of this study was to identify core genes and pathways involved in the pathogenesis of LN. Methods We screened differentially expressed genes (DEGs) in LN patients using mRNA expression profile data from the Gene Expression Omnibus. The functional and pathway enrichment analysis of DEGs was performed utilizing the Database for annotation, Visualization and Integrated Discovery. Target genes with differentially expressed miRNAs (DEMIs) were predicted using the miRTarBase database, and the intersection between these target genes and DEGs was selected to be studied further. Results In total, 107 common DEGs (CDEGs) were identified from the Tub_LN group and Glom_LN group, and 66 DEMIs were identified. Fifty-three hub genes and two significant modules were identified from the protein–protein interaction (PPI) network, and a miRNA–mRNA network was constructed. The CDEGs, module genes in the PPI network and genes intersecting with the CDEGs and target genes of DEMIs were all associated with the PI3K-Akt signalling pathway. Conclusion In summary, this study reveals some crucial genes and pathways potentially involving in the pathogenesis of LN. These findings provide a new insight for the research and treatment of LN.

Download Full-text

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.

Download Full-text

Identification and characterization of critical genes associated with tamoxifen resistance in breast cancer

PeerJ ◽

10.7717/peerj.10468 ◽

2020 ◽

Vol 8 ◽

pp. e10468

Author(s):

Kai Zhang ◽

Kuikui Jiang ◽

Ruoxi Hong ◽

Fei Xu ◽

Wen Xia ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Target Genes ◽

Expression Profiles ◽

Tamoxifen Resistance ◽

Gene Expression Profiles ◽

Gene Expression Omnibus ◽

Ppi Network ◽

Hub Genes ◽

Mcf 7

Background Tamoxifen resistance in breast cancer is an unsolved problem in clinical practice. The aim of this study was to determine the potential mechanisms of tamoxifen resistance through bioinformatics analysis. Methods Gene expression profiles of tamoxifen-resistant MCF-7/TR and MCF-7 cells were acquired from the Gene Expression Omnibus dataset GSE26459, and differentially expressed genes (DEGs) were detected with R software. We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses using Database for Annotation, Visualization and Integrated Discovery. A protein–protein interaction (PPI) network was generated, and we analyzed hub genes in the network with the Search Tool for the Retrieval of Interacting Genes database. Finally, we used siRNAs to silence the target genes and conducted the MTS assay. Results We identified 865 DEGs, 399 of which were upregulated. GO analysis indicated that most genes are related to telomere organization, extracellular exosomes, and binding-related items for protein heterodimerization. PPI network construction revealed that the top 10 hub genes—ACLY, HSPD1, PFAS, GART, TXN, HSPH1, HSPE1, IRAS, TRAP1, and ATIC—might be associated with tamoxifen resistance. Consistently, RT-qPCR analysis indicated that the expression of these 10 genes was increased in MCF-7/TR cells comparing with MCF-7 cells. Four hub genes (TXN, HSPD1, HSPH1 and ATIC) were related to overall survival in patients who accepted tamoxifen. In addition, knockdown of HSPH1 by siRNA may lead to reduced growth of MCF-7/TR cell with a trend close to significance (P = 0.07), indicating that upregulation of HSPH1 may play a role in tamoxifen resistance. Conclusion This study revealed a number of critical hub genes that might serve as therapeutic targets in breast cancer resistant to tamoxifen and provided potential directions for uncovering the mechanisms of tamoxifen resistance.

Download Full-text

Genome-wide transcriptome profiling uncovers differential miRNAs and lncRNAs in ovaries of Hu sheep at different developmental stages

Scientific Reports ◽

10.1038/s41598-021-85245-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Samina Shabbir ◽

Prerona Boruah ◽

Lingli Xie ◽

Muhammad Fakhar-e-Alam Kulyar ◽

Mohsin Nawaz ◽

...

Keyword(s):

Target Genes ◽

Expression Profiles ◽

Ovarian Follicle ◽

Follicular Development ◽

Differentially Expressed ◽

Ovary Development ◽

Estrogen Metabolism ◽

Genome Wide ◽

Micro Rnas ◽

Hu Sheep

AbstractOvary development is an important determinant of the procreative capacity of female animals. Here, we performed genome-wide sequencing of long non-coding RNAs (lncRNAs) and mRNAs on ovaries of 1, 3 and 8 months old Hu sheep to assess their expression profiles and roles in ovarian development. We identified 37,309 lncRNAs, 45,404 messenger RNAs (mRNAs) and 330 novel micro RNAs (miRNAs) from the transcriptomic analysis. Six thousand, seven hundred and sixteen (6716) mRNAs and 1972 lncRNAs were significantly and differentially expressed in ovaries of 1 month and 3 months old Hu sheep (H1 vs H3). These mRNAs and target genes of lncRNAs were primarily enriched in the TGF-β and PI3K-Akt signalling pathways which are closely associated with ovarian follicular development and steroid hormone biosynthesis regulation. We identified MSTRG.162061.1, MSTRG.222844.7, MSTRG.335777.1, MSTRG.334059.16, MSTRG.188947.6 and MSTRG.24344.3 as vital genes in ovary development by regulating CTNNB1, CCNA2, CDK2, CDC20, CDK1 and EGFR expressions. A total of 2903 mRNAs and 636 lncRNAs were differentially expressed in 3 and 8 months old ovaries of Hu sheep (H3 vs H8); and were predominantly enriched in PI3K-Akt, progesterone-mediated oocyte maturation, estrogen metabolism, ovulation from the ovarian follicle and oogenesis pathways. These lncRNAs were also found to regulate FGF7, PRLR, PTK2, AMH and INHBA expressions during follicular development. Our result indicates the identified genes participate in the development of the final stages of follicles and ovary development in Hu sheep.

Download Full-text

Comprehensive analysis of IgA nephropathy expression profiles: identification of potential biomarkers and therapeutic agents

BMC Nephrology ◽

10.1186/s12882-021-02356-4 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Alieh Gholaminejad ◽

Yousof Gheisari ◽

Sedigheh Jalali ◽

Amir Roointan

Keyword(s):

Iga Nephropathy ◽

Regulatory Network ◽

Target Genes ◽

Expression Profiles ◽

Gene Signature ◽

Gene Expression Omnibus ◽

Integrative Approach ◽

Potential Factors ◽

Ngf Signaling ◽

Underlying Mechanisms

Abstract Background IgA nephropathy (IgAN) is a kidney disease recognized by the presence of IgA antibody depositions in kidneys. The underlying mechanisms of this complicated disease are remained to be explored and still, there is an urgent need for the discovery of noninvasive biomarkers for its diagnosis. In this investigation, an integrative approach was applied to mRNA and miRNA expression profiles in PBMCs to discover a gene signature and novel potential targets/biomarkers in IgAN. Methods Datasets were selected from gene expression omnibus database. After quality control checking, two datasets were analyzed by Limma to identify differentially expressed genes/miRNAs (DEGs and DEmiRs). Following identification of DEmiR-target genes and data integration, intersecting mRNAs were subjected to different bioinformatic analyses. The intersecting mRNAs, DEmiRs, related transcription factors (from TRRUST database), and long-non coding RNAs (from LncTarD database) were used for the construction of a multilayer regulatory network via Cytoscape. Result “GSE25590” (miRNA) and “GSE73953” (mRNA) datasets were analyzed and after integration, 628 intersecting mRNAs were identified. The mRNAs were mainly associated with “Innate immune system”, “Apoptosis”, as well as “NGF signaling” pathways. A multilayer regulatory network was constructed and several hub-DEGs (Tp53, STAT3, Jun, etc.), DEmiRs (miR-124, let-7b, etc.), TFs (NF-kB, etc.), and lncRNAs (HOTAIR, etc.) were introduced as potential factors in the pathogenesis of IgAN. Conclusion Integration of two different expression datasets and construction of a multilayer regulatory network not only provided a deeper insight into the pathogenesis of IgAN, but also introduced several key molecules as potential therapeutic target/non-invasive biomarkers.

Download Full-text

Identification of Tumorigenic and Prognostic Biomarkers in Colorectal Cancer Based on microRNA Expression Profiles

BioMed Research International ◽

10.1155/2020/7136049 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Yuntao Shi ◽

Yingying Zhuang ◽

Jialing Zhang ◽

Mengxue Chen ◽

Shangnong Wu

Keyword(s):

Target Genes ◽

Cox Regression ◽

Expression Profiles ◽

Survival Rates ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Risk Groups ◽

Normal Mucosa ◽

Microrna Expression ◽

Functional Enrichment

Objective. Although noncoding RNAs, especially the microRNAs, have been found to play key roles in CRC development in intestinal tissue, the specific mechanism of these microRNAs has not been fully understood. Methods. GEO and TCGA database were used to explore the microRNA expression profiles of normal mucosa, adenoma, and carcinoma. And the differential expression genes were selected. Computationally, we built the SVM model and multivariable Cox regression model to evaluate the performance of tumorigenic microRNAs in discriminating the adenomas from normal tissues and risk prediction. Results. In this study, we identified 20 miRNA biomarkers dysregulated in the colon adenomas. The functional enrichment analysis showed that MAPK activity and MAPK cascade were highly enriched by these tumorigenic microRNAs. We also investigated the target genes of the tumorigenic microRNAs. Eleven genes, including PIGF, TPI1, KLF4, RARS, PCBP2, EIF5A, HK2, RAVER2, HMGN1, MAPK6, and NDUFA2, were identified to be frequently targeted by the tumorigenic microRNAs. The high AUC value and distinct overall survival rates between the two risk groups suggested that these tumorigenic microRNAs had the potential of diagnostic and prognostic value in CRC. Conclusions. The present study revealed possible mechanisms and pathways that may contribute to tumorigenesis of CRC, which could not only be used as CRC early detection biomarkers, but also be useful for tumorigenesis mechanism studies.

Download Full-text

Characterization of Differentially Expressed miRNAs by CXCL12/SDF-1 in Human Bone Marrow Stromal Cells

BioMolecular Concepts ◽

10.1515/bmc-2021-0015 ◽

2021 ◽

Vol 12 (1) ◽

pp. 132-143

Author(s):

Matthew L. Potter ◽

Kathryn Smith ◽

Sagar Vyavahare ◽

Sandeep Kumar ◽

Sudharsan Periyasamy-Thandavan ◽

...

Keyword(s):

Bone Marrow ◽

Fracture Healing ◽

Osteogenic Differentiation ◽

Stromal Cell ◽

Target Genes ◽

Fatty Acid Biosynthesis ◽

Gene Expression Omnibus ◽

Differentially Expressed ◽

Mirna Regulation ◽

Stromal Cell Derived Factor

Abstract Stromal cell-derived factor 1 (SDF-1) is known to influence bone marrow stromal cell (BMSC) migration, osteogenic differentiation, and fracture healing. We hypothesize that SDF-1 mediates some of its effects on BMSCs through epigenetic regulation, specifically via microRNAs (miRNAs). MiRNAs are small non-coding RNAs that target specific mRNA and prevent their translation. We performed global miRNA analysis and determined several miRNAs were differentially expressed in response to SDF-1 treatment. Gene Expression Omnibus (GEO) dataset analysis showed that these miRNAs play an important role in osteogenic differentiation and fracture healing. KEGG and GO analysis indicated that SDF-1 dependent miRNAs changes affect multiple cellular pathways, including fatty acid biosynthesis, thyroid hormone signaling, and mucin-type O-glycan biosynthesis pathways. Furthermore, bioinformatics analysis showed several miRNAs target genes related to stem cell migration and differentiation. This study's findings indicated that SDF-1 induces some of its effects on BMSCs function through miRNA regulation.

Download Full-text

Identifcation of The Ferroptosis-Related Gene Signature In Placenta of Patients With Early-Onset Preeclampsia

10.21203/rs.3.rs-618453/v1 ◽

2021 ◽

Author(s):

Nana Yang ◽

Qianghua Wang ◽

Biao Ding ◽

Yinging Gong ◽

Yue Wu ◽

...

Keyword(s):

Iron Homeostasis ◽

Molecular Mechanisms ◽

Late Onset ◽

Expression Profiles ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Differentially Expressed ◽

Ppi Network ◽

Network Analyses

Abstract Background: The accumulation of ROS resulting from upregulated levels of oxidative stress is commonly implicated in preeclampsia (PE). Ferroptosis is a novel form of iron-dependent cell death instigated by lipid peroxidation likely plays important role in PE pathogenesis. This study aims to investigate expression profiles and functions of the ferroptosis-related genes (FRGs) in early- and late-onset preeclampsia.Methods: The gene expression data and clinical information were downloaded from GEO database. The “limma” R package was used for screening differentially expressed genes. GO(Gene Ontology), Kyoto Encyclopedia of Genes and Genomes(KEGG) and protein protein interaction (PPI) network analyses were conducted to investigate the bioinformatics functions and molecular interactions of significantly different FRGs. Quantitative real-time reverse transcriptase PCR was used to verify the expression of hub FRGs in PE.Results: A total number of 4,215 DEGs were identified between EOPE and preterm cases and 3,356 DEGs were found between EOPE and LOPE subtypes. 20 significantly different FRGs were identified in EOPE, while only 3 in LOPE. Functional enrichment analysis revealed that the differentially expressed FRGs was mainly involved in EOPE and enriched in hypoxia- and iron-related pathways, such as response to hypoxia, iron homeostasis and iron ion binding process. The PPI network analysis and verification by RT-qPCR resulted in the identification of the following six interesting FRGs: FTH1, HIF1A, FTL, IREB2, MAPK8 and PLIN2. Conclusions: EOPE and LOPE owned distinct underlying molecular mechanisms and ferroptosis may be mainly implicated in pathogenesis of EOPE. Further studies are necessary for deeper inquiry into placental ferroptosis and its role in the pathogenesis of EOPE.

Download Full-text

Identification of Key miRNAs in the Treatment of Dabrafenib-Resistant Melanoma

BioMed Research International ◽

10.1155/2021/5524486 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Guangyu Gao ◽

Zhen Yao ◽

Jiaofeng Shen ◽

Yulong Liu

Keyword(s):

Drug Resistance ◽

Molecular Mechanism ◽

Target Genes ◽

Enrichment Analysis ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Pathway Enrichment Analysis ◽

Ppi Network ◽

Protein Protein Interaction ◽

Obvious Association

Dabrafenib resistance is a significant problem in melanoma, and its underlying molecular mechanism is still unclear. The purpose of this study is to research the molecular mechanism of drug resistance of dabrafenib and to explore the key genes and pathways that mediate drug resistance in melanoma. GSE117666 was downloaded from the Gene Expression Omnibus (GEO) database and 492 melanoma statistics were also downloaded from The Cancer Genome Atlas (TCGA) database. Besides, differentially expressed miRNAs (DEMs) were identified by taking advantage of the R software and GEO2R. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) and FunRich was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to identify potential pathways and functional annotations linked with melanoma chemoresistance. 9 DEMs and 872 mRNAs were selected after filtering. Then, target genes were uploaded to Metascape to construct protein-protein interaction (PPI) network. Also, 6 hub mRNAs were screened after performing the PPI network. Furthermore, a total of 4 out of 9 miRNAs had an obvious association with the survival rate ( P < 0.05 ) and showed a good power of risk prediction model of over survival. The present research may provide a deeper understanding of regulatory genes of dabrafenib resistance in melanoma.

Download Full-text

Effects of MiR-451a on the Phagocytosis and Polarization of Macrophages

Blood ◽

10.1182/blood-2020-140250 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 42-42

Author(s):

Xiaoli Liu ◽

Dongyue Zhang ◽

Hao Wang ◽

Qian Ren ◽

Lina Wang ◽

...

Keyword(s):

Bone Marrow ◽

Conflicts Of Interest ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Microrna Expression ◽

Differentially Expressed ◽

Proliferation Capacity ◽

Microrna Sequencing ◽

Differentiation Marker

Macrophages are important member in tissue microenvironments and play diverse physiologic and pathologic roles. Leukemia associated macrophages (LAM) are a kind of specifically activated macrophages in leukemia microenvironment, which are different from M1, M2 and TAMs. We have reported the heterogeneities in gene expression profiles of LAMs. However, MicroRNA expression profiles of LAMs and regulatory mechanism are still unknown. Here, a MLL-AF9 induced mouse acute myeloid leukemia (AML) model was used, and LAMs in the spleen and bone marrow were sorted for microRNA sequencing. The microRNA expression profiles of LAMs in bone marrow and spleen in AML mice were different from macrophages from control mice. Based on the volcano plot, more than 100 microRNAs were differentially expressed in LAMs compared with macrophages in control mice. Next, five differentially expressed microRNAs were selected and verified by qRT-PCR in LAMs from spleen. The results showed that miR-451a and miR-155-5p in spleen LAMs were significantly upregulated in LAMs from spleen. Overexpression of miR-451a altered the morphology of macrophages, enhanced the phagocytic ability of macrophages, and promotes the expression of macrophage differentiation marker CD11b. Furthermore, overexpression of miR-451a had little effect on M0 macrophages, but increased the proliferation capacity of macrophages upon stimulation toward M1 or M2 phenotype. MiR-451a overexpressed-macrophages had higher level of iNOS when stimulated with LPS or IL-4 whereas there was no difference in the expression of IL-1β, IL-6, CD206 and Arg-1 between MiR-451a overexpressed-macrophages and control macrophage. Therefore, our data revealed the characteristics of the microRNA expression profile of LAMs for the first time, and verified the effect of miR-451a on macrophage in vitro. Disclosures No relevant conflicts of interest to declare.

Download Full-text