Differentially Expressed miRNAs in Hepatocellular Carcinoma Target Genes in the Genetic Information Processing and Metabolism Pathways

Abstract Background: Hepatocellular carcinoma (HCC) is one of the most malignant tumors in the world. The pathogenesis of HCC is complex and closely related to chronic uncontrollable inflammation. As a bridge between inflammation and cancer, circulating exosomes play a vital role in early tumorigenesis, metastasis, and immune escape. Studies have shown that exosomes containing specific RNAs may be potential diagnostic and therapeutic targets for HCC. Purpose The current research investigated key circRNA through exosome-derived competitive endogenous RNA network based on the ExoRBase database. Methods: The circRNA, lncRNA, and mRNA expression profiles of human blood samples were downloaded from the ExoRBase database. At the standard of P<0.05 and log FC>0, differentially expressed genes (DEGs) were further identified between normal human and HCC patients. The co-expressed pairs of DEGs were predicted by TargetScan, miRcode, and StarBase databases. The ceRNA network was constructed by Cytoscape software. Subsequently, target genes corresponding to circRNA in the ceRNA network were annotated and analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG). The potential transcription factors were screened by FunRich database. Results: At the criterion of P<0.05 and log FC>0, 13 differentially expressed circRNAs(DECs) were identified with 9 up-regulated and 4 down-regulated. The co-expressed differentially expressed miRNAs-mRNAs (DEMis-DEMs) (620 pairs), differentially expressed miRNAs- LncRNAs (DEMis-DElncRNA) (684 pairs) and DEMis-DECs (53 pairs) were finally predicted to construct the ceRNA network. The GO analysis indicated that target genes in the ceRNA network were mainly enriched in the molecular function of protein serine/threonine kinase activity. KEGG pathway analysis suggested target genes were enriched in two pathways of MAPK and central carbon metabolism. Conclusion: The study provides a valuable reference for HCC through the ceRNA network in exosomes. Besides, hsa_circ_0000284 may be potential diagnostic markers of HCC.

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Investigation of the miRNA and mRNA Coexpression Network and Their Prognostic Value in Hepatocellular Carcinoma

BioMed Research International ◽

10.1155/2020/8726567 ◽

2020 ◽

Vol 2020 ◽

pp. 1-19

Author(s):

Hao Zhang ◽

Xi Chen ◽

Yufeng Yuan

Keyword(s):

Hepatocellular Carcinoma ◽

Gene Ontology ◽

Cell Adhesion ◽

Target Genes ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Positive Regulation ◽

Differentially Expressed Mirnas ◽

Cell Cell

Purpose. To identify pivotal differentially expressed miRNAs and genes and construct their regulatory network in hepatocellular carcinoma. Methods. mRNA (GSE101728) and microRNA (GSE108724) microarray datasets were obtained from the NCBI Gene Expression Omnibus (GEO) database. Then, we identified the differentially expressed miRNAs and mRNAs. Sequentially, transcription factor enrichment and gene ontology (GO) enrichment analysis for miRNA were performed. Target genes of these differential miRNAs were obtained using packages in R language ( R package multiMiR). After that, downregulated miRNAs were matched with target mRNAs which were upregulated, while upregulated miRNAs were paired with downregulated target mRNA using scripts written in Perl. An miRNA-mRNA network was constructed and visualized in Cytoscape software. For miRNAs in the network, survival analysis was performed. And for genes in the network, we did gene ontology (GO) and KEGG pathway enrichment analysis. Results. A total of 35 miRNAs and 295 mRNAs were involved in the network. These differential genes were enriched in positive regulation of cell-cell adhesion, positive regulation of leukocyte cell-cell adhesion, and so on. Eight differentially expressed miRNAs were found to be associated with the OS of patients with HCC. Among which, miR-425 and miR-324 were upregulated while the other six, including miR-99a, miR-100, miR-125b, miR-145, miR-150, and miR-338, were downregulated. Conclusion. In conclusion, these results can provide a potential research direction for further studies about the mechanisms of how miRNA affects malignant behavior in hepatocellular carcinoma.

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Does a Ribosome Really Read? On the Cognitive Roots and Heuristic Value of Linguistic Metaphors in Molecular Genetics. Part 2

Russian Journal of Philosophical Sciences ◽

10.30727/0235-1188-2020-63-2-46-62 ◽

2020 ◽

Vol 63 (2) ◽

pp. 46-62

Author(s):

Suren T. Zolyan

Keyword(s):

Information Processing ◽

Genetic Information ◽

Formal Organization ◽

Dual Nature ◽

Reading Frame ◽

The Core ◽

Genetic Information Processing ◽

Cognitive Frame ◽

Effective Instrument

We discuss the role of linguistic metaphors as a cognitive frame for the understanding of genetic information processing. The essential similarity between language and genetic information processing has been recognized since the very beginning, and many prominent scholars have noted the possibility of considering genes and genomes as texts or languages. Most of the core terms in molecular biology are based on linguistic metaphors. The processing of genetic information is understood as some operations on text – writing, reading and editing and their specification (encoding/decoding, proofreading, transcription, translation, reading frame). The concept of gene reading can be traced from the archaic idea of the equation of Life and Nature with the Book. Thus, the genetics itself can be metaphorically represented as some operations on text (deciphering, understanding, code-breaking, transcribing, editing, etc.), which are performed by scientists. At the same time linguistic metaphors portrayed gene entities also as having the ability of reading. In the case of such “bio-reading” some essential features similar to the processes of human reading can be revealed: this is an ability to identify the biochemical sequences based on their function in an abstract system and distinguish between type and its contextual tokens of the same type. Metaphors seem to be an effective instrument for representation, as they make possible a two-dimensional description: biochemical by its experimental empirical results and textual based on the cognitive models of comprehension. In addition to their heuristic value, linguistic metaphors are based on the essential characteristics of genetic information derived from its dual nature: biochemical by its substance, textual (or quasi-textual) by its formal organization. It can be concluded that linguistic metaphors denoting biochemical objects and processes seem to be a method of description and explanation of these heterogeneous properties.

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Bioinformatics Analysis Reveals Functions of MicroRNAs in Rice Under the Drought Stress

Current Bioinformatics ◽

10.2174/1574893615666200207092410 ◽

2021 ◽

Vol 15 (8) ◽

pp. 927-936 ◽

Cited By ~ 3

Author(s):

Yan Peng ◽

Yuewu Liu ◽

Xinbo Chen

Keyword(s):

Drought Stress ◽

Target Genes ◽

Hot Spot ◽

Interaction Network ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Protein Protein Interaction ◽

Promising Tool ◽

Differentially Expressed Mirnas ◽

Aba Biosynthesis

Background: Drought is one of the most damaging and widespread abiotic stresses that can severely limit the rice production. MicroRNAs (miRNAs) act as a promising tool for improving the drought tolerance of rice and have become a hot spot in recent years. Objective: In order to further extend the understanding of miRNAs, the functions of miRNAs in rice under drought stress are analyzed by bioinformatics. Method: In this study, we integrated miRNAs and genes transcriptome data of rice under the drought stress. Some bioinformatics methods were used to reveal the functions of miRNAs in rice under drought stress. These methods included target genes identification, differentially expressed miRNAs screening, enrichment analysis of DEGs, network constructions for miRNA-target and target-target proteins interaction. Results: (1) A total of 229 miRNAs with differential expression in rice under the drought stress, corresponding to 73 rice miRNAs families, were identiﬁed. (2) 1035 differentially expressed genes (DEGs) were identified, which included 357 up-regulated genes, 542 down-regulated genes and 136 up/down-regulated genes. (3) The network of regulatory relationships between 73 rice miRNAs families and 1035 DEGs was constructed. (4) 25 UP_KEYWORDS terms of DEGs, 125 GO terms and 7 pathways were obtained. (5) The protein-protein interaction network of 1035 DEGs was constructed. Conclusion: (1) MiRNA-regulated targets in rice might mainly involve in a series of basic biological processes and pathways under drought conditions. (2) MiRNAs in rice might play critical roles in Lignin degradation and ABA biosynthesis. (3) MiRNAs in rice might play an important role in drought signal perceiving and transduction.

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MicroRNA sequence analysis identifies microRNAs associated with peri-implantitis in dogs

Bioscience Reports ◽

10.1042/bsr20170768 ◽

2017 ◽

Vol 37 (5) ◽

Cited By ~ 10

Author(s):

Xiaolin Wu ◽

Xipeng Chen ◽

Wenxiang Mi ◽

Tingting Wu ◽

Qinhua Gu ◽

...

Keyword(s):

Sequence Analysis ◽

Target Genes ◽

Alveolar Bone ◽

Biological Effects ◽

Bone Destruction ◽

Mapk Signaling ◽

Differentially Expressed ◽

Mitogen Activated Protein Kinase ◽

Mirna Sequence ◽

Differentially Expressed Mirnas

Peri-implantitis, which is characterized by dense inflammatory infiltrates and increased osteoclast activity, can lead to alveolar bone destruction and implantation failure. miRNAs participate in the regulation of various inflammatory diseases, such as periodontitis and osteoporosis. Therefore, the present study aimed to investigate the differential expression of miRNAs in canine peri-implantitis and to explore the functions of their target genes. An miRNA sequence analysis was used to identify differentially expressed miRNAs in peri-implantitis. Under the criteria of a fold-change >1.5 and P<0.01, 8 up-regulated and 30 down-regulated miRNAs were selected for predictions of target genes and their biological functions. Based on the results of Gene Ontology (GO) and KEGG pathway analyses, these miRNAs may fine-tune the inflammatory process in peri-implantitis through an intricate mechanism. The results of quantitative real-time PCR (qRT-PCR) revealed that let-7g, miR-27a, and miR-145 may play important roles in peri-implantitis and are worth further investigation. The results of the present study provide insights into the potential biological effects of the differentially expressed miRNAs, and specific enrichment of target genes involved in the mitogen-activated protein kinase (MAPK) signaling pathway was observed. These findings highlight the intricate and specific roles of miRNAs in inflammation and osteoclastogenesis, both of which are key aspects of peri-implantitis, and thus may contribute to future investigations of the etiology, underlying mechanism, and treatment of peri-implantitis.

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Identification of New miRNA-mRNA Networks in the Development of Non-syndromic Cleft Lip With or Without Cleft Palate

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.631057 ◽

2021 ◽

Vol 9 ◽

Author(s):

Chengyi Fu ◽

Shu Lou ◽

Guirong Zhu ◽

Liwen Fan ◽

Xin Yu ◽

...

Keyword(s):

Cell Proliferation ◽

Cleft Palate ◽

Negative Correlation ◽

Cell Apoptosis ◽

Cleft Lip ◽

Target Genes ◽

Craniofacial Development ◽

Differentially Expressed ◽

Differentially Expressed Mirnas

Objective: To identify new microRNA (miRNA)-mRNA networks in non-syndromic cleft lip with or without cleft palate (NSCL/P).Materials and Methods: Overlapping differentially expressed miRNAs (DEMs) were selected from cleft palate patients (GSE47939) and murine embryonic orofacial tissues (GSE20880). Next, the target genes of DEMs were predicted by Targetscan, miRDB, and FUNRICH, and further filtered through differentially expressed genes (DEGs) from NSCL/P patients and controls (GSE42589), MGI, MalaCards, and DECIPHER databases. The results were then confirmed by in vitro experiments. NSCL/P lip tissues were obtained to explore the expression of miRNAs and their target genes.Results: Let-7c-5p and miR-193a-3p were identified as DEMs, and their overexpression inhibited cell proliferation and promoted cell apoptosis. PIGA and TGFB2 were confirmed as targets of let-7c-5p and miR-193a-3p, respectively, and were involved in craniofacial development in mice. Negative correlation between miRNA and mRNA expression was detected in the NSCL/P lip tissues. They were also associated with the occurrence of NSCL/P based on the MGI, MalaCards, and DECIPHER databases.Conclusions: Let-7c-5p-PIGA and miR-193a-3p-TGFB2 networks may be involved in the development of NSCL/P.

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Identification of cold stress responsive microRNAs in cold tolerant and susceptible Hemerocallis fulva by high throughput sequencing

10.21203/rs.3.rs-41470/v1 ◽

2020 ◽

Author(s):

Changbing Huang ◽

Chun Jiang ◽

limin Jin ◽

Huanchao Zhang

Keyword(s):

Low Temperature ◽

Cold Stress ◽

Cold Tolerance ◽

Temperature Stress ◽

Stress Responses ◽

Target Genes ◽

Low Temperature Stress ◽

Differentially Expressed ◽

Differentially Expressed Mirnas ◽

Cold Tolerant

Abstract Background:Hemerocallis fulva is a perennial herb belonging to Hemerocallis of Hemerocallis. Because of the large and bright colors, it is often used as a garden ornamental plant. But most varieties of H. fulva on the market will wither in winter, which will affect their beauty. It is very important to study the effect of low temperature stress on the physiological indexes of H. fulva and understand the cold tolerance of different H. fulva. MiRNA is a kind of endogenous non coding small molecular RNA with length of 21-24nt. It mainly inhibits protein translation by cutting target genes, and plays an important role in the development of organisms, gene expression and biological stress. Low temperature is the main abiotic stress affecting the production of H. fulva in China, which hinders the growth and development of plants. A comprehensive understanding of the expression pattern of microRNA in H. fulva under low temperature stress can improve our understanding of microRNA mediated stress response. Although there are many studies on miRNAs of various plants under cold stress at home and abroad, there are few studies on miRNAs related to cold stress of H. fulva. It is of great significance to explore the cold stress resistant gene resources of H. fulva, especially the identification and functional research of miRNA closely related to cold stress, for the breeding of excellent H. fulva.Results A total of 5619 cold-responsive miRNAs, 315 putative novel and 5 304 conserved miRNAs, were identified from the leaves and roots of two different varieties ‘Jinyan’ (cold-tolerant) and ‘Lucretius ’ (cold-sensitive), which were stressed under -4 oC for 24 h. Twelve conserved and three novel miRNAs (novel-miR10, novel-miR19 and novel-miR48) were differentially expressed in leaves of ‘Jinyan’ under cold stress. Novel-miR19, novel-miR29 and novel-miR30 were up-regulated in roots of ‘Jinyan’ under cold stress. Thirteen and two conserved miRNAs were deferentially expressed in leaves and roots of ‘Lucretius’ after cold stress. The deferentially expressed miRNAs between two cultivars under cold stress include novel miRNAs and the members of the miR156, miR166 and miR319 families. A total of 6 598 target genes for 6 516 known miRNAs and 82 novel miRNAs were predicted by bioinformatic analysis, mainly involved in metabolic processes and stress responses. Ten differentially expressed miRNAs and predicted target genes were confirmed by quantitative reverse transcription PCR(q-PCR), and the expressional changes of target genes were negatively correlated to differentially expressed miRNAs. Our data indicated that some candidate miRNAs (e.g., miR156a-3-p, miR319a, and novel-miR19) may play important roles in plant response to cold stress.Conclusions Our study indicates that some putative target genes and miRNA mediated metabolic processes and stress responses are significant to cold tolerance in H. fulva.

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Construction and validation of a novel prognostic signature of microRNAs in lung adenocarcinoma

PeerJ ◽

10.7717/peerj.10470 ◽

2021 ◽

Vol 9 ◽

pp. e10470

Author(s):

Wanzhen Li ◽

Shiqing Liu ◽

Shihong Su ◽

Yang Chen ◽

Gengyun Sun

Keyword(s):

Lung Adenocarcinoma ◽

Signaling Pathway ◽

Prognostic Value ◽

Target Genes ◽

Predictive Accuracy ◽

Differentially Expressed ◽

Prognostic Signature ◽

Tissue Samples ◽

Gene Set ◽

Differentially Expressed Mirnas

MicroRNA (miRNA, miR) has been reported to be highly implicated in a wide range of biological processes in lung cancer (LC), and identification of differentially expressed miRNAs between normal and LC samples has been widely used in the discovery of prognostic factors for overall survival (OS) and response to therapy. The present study was designed to develop and evaluate a miRNA-based signature with prognostic value for the OS of lung adenocarcinoma (LUAD), a common histologic subtype of LC. In brief, the miRNA expression profiles and clinicopathological factors of 499 LUAD patients were collected from The Cancer Genome Atlas (TCGA) database. Kaplan–Meier (K-M) survival analysis showed significant correlations between differentially expressed miRNAs and LUAD survival outcomes. Afterward, 1,000 resample LUAD training matrices based on the training set was applied to identify the potential prognostic miRNAs. The least absolute shrinkage and selection operator (LASSO) cox regression analysis was used to constructed a six-miRNA based prognostic signature for LUAD patients. Samples with different risk scores displayed distinct OS in K-M analysis, indicating considerable predictive accuracy of this signature in both training and validation sets. Furthermore, time-dependent receiver operating characteristic (ROC) analysis demonstrated the nomogram achieved higher predictive accuracy than any other clinical variables after incorporating the clinical information (age, sex, stage, and recurrence). In the stratification analysis, the prognostic value of this classifier in LUAD patients was validated to be independent of other clinicopathological variables, such as age, gender, tumor recurrence, and early stage. Gene set annotation analyses were also conducted through the Hallmark gene set and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, indicating target genes of the six miRNAs were positively related to various molecular pathways of cancer, such as hallmark UV response, Wnt signaling pathway and mTOR signaling pathway. In addition, fresh cancer tissue samples and matched adjacent tissue samples from 12 LUAD patients were collected to verify the expression of miR-582’s target genes in the model, further revealing the potential relationship between SOX9, RASA1, CEP55, MAP4K4 and LUAD tumorigenesis, and validating the predictive value of the model. Taken together, the present study identified a robust signature for the OS prediction of LUAD patients, which could potentially aid in the individualized selection of therapeutic approaches for LUAD patients.

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Plasma-Derived Exosomal hsa-miR-4488 and hsa-miR-1228-5p: Novel Biomarkers for Dermatomyositis-Associated Interstitial Lung Disease with Anti-Melanoma Differentiation-Associated Protein 5 Antibody-Positive Subset

BioMed Research International ◽

10.1155/2021/6676107 ◽

2021 ◽

Vol 2021 ◽

pp. 1-16

Author(s):

Danli Zhong ◽

Chanyuan Wu ◽

Dong Xu ◽

Jingjing Bai ◽

Qian Wang ◽

...

Keyword(s):

Interstitial Lung Disease ◽

Lung Disease ◽

Target Genes ◽

Homo Sapiens ◽

Differentially Expressed ◽

Transmission Electron ◽

Exosomal Mirnas ◽

Differentially Expressed Mirnas ◽

Novel Biomarkers ◽

And Gender

The present study is aimed at profiling circulating exosome-derived microRNAs (miRNAs/miRs) from patients with dermatomyositis (DM), in particular those complicated with interstitial lung disease (ILD) with anti-melanoma differentiation-associated protein 5 (MDA5) antibody-positive. Fifteen participants were enrolled, including five patients with DM complicated with ILDs prior to treatment with circulating anti-MDA5 antibody-positive status [DM-ILD-MDA5 Ab(+)], five DM patients without ILDs who were negative for 16 detectable myositis-specific antibodies [DM-nonILD-MSA16(-)], and five age- and gender-matched healthy donor controls (HCs). The characteristics of the exosomes extracted by Ribo™ Exosome Isolation Reagent were identified using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and flow cytometry. Differentially expressed miRNAs, determined by next-generation deep sequencing, were identified through the criteria of ∣ log 2 fold change ∣ ≥ 1 and P < 0.01 . A total of 38 miRNAs were significantly upregulated in exosomes from patients with DM-ILD-MDA5 Ab(+) compared to those from HC, while 21 miRNAs were significantly downregulated. Compared to exosomes derived from patients with DM-nonILD-MSA16(-), 51 miRNAs were significantly upregulated and 33 miRNAs were significantly downregulated from patients with DM-ILD-MDA5 Ab(+). A total of 73 exosomal miRNAs were significantly differentially expressed between DM-nonILD-MSA16(-) and HC. In particular, two miRNAs, Homo sapiens- (hsa-) miR-4488 and hsa-miR-1228-5p, were common differentially expressed miRNAs among three comparisons. GO and KEGG analyses suggested that several pathways may contribute the pathogenesis of DM-ILD-MDA5 Ab(+) and DM-nonILD-MSA16(-), while PPI network analysis of hsa-miR-4488 and hsa-miR-1228-5p indicated that their predicted target genes, DExD-box helicase 39B and MDM2, may be involved in the mechanisms of DM-ILD-MDA5 Ab(+).

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The New Synthesis

Creatures of Cain ◽

10.23943/princeton/9780691181882.003.0014 ◽

2018 ◽

pp. 235-245

Author(s):

Erika Lorraine Milam

Keyword(s):

Sexual Selection ◽

Information Processing ◽

Human Nature ◽

Genetic Information ◽

Next Generation ◽

New Synthesis ◽

Genetic Information Processing ◽

The 1960S ◽

Natural And Sexual Selection

This chapter discusses new understandings of humanity from the 1960s onward. It shows how a particular group of scientists struggled with the question of human nature by conceiving of natural and sexual selection as acting at the level of individuals, who in turn served as genetic-information processing units. A trait could not spread in a population unless it conferred some advantage to the individuals who possessed it, allowing them to contribute more copies of their genes to the next generation of that population than other individuals. These struggles are furthermore framed within a period when sociobiology was just starting to get a foothold in academics.

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