Integrated Analysis of Differentially Expressed Genes and Construction of a Competing Endogenous RNA Network in Human Huntington Neural Progenitor Cells

Abstract Background Huntington's disease (HD) is one of the most common polyglutamine disorders, leading to progressive dyskinesia, cognitive impairment, and neuropsychological problems. Besides the dysregulation of many protein-coding genes in HD, previous studies have revealed a variety of non-coding RNAs that are dysregulated in HD, including several long non-coding RNAs (lncRNAs). However, an integrated analysis of differentially expressed (DE) genes based on a competing endogenous RNA (ceRNA) network is still currently lacking. Results Here, we have systematically analyzed the gene expression profile data of neural progenitor cells (NPCs) derived from patients with HD and controls (healthy controls and the isogenic controls of HD patient cell lines corrected using CRISPR-Cas9 approach at the HTT locus, and we identified 490 DE mRNAs and 94 DE lncRNAs, respectively. Of these, 189 mRNAs and 20 lncRNAs were applied to create a ceRNA network. To learn more about the possible functions of lncRNAs in the ceRNA regulatory network in HD, we conducted a functional analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) and established a protein-protein interaction (PPI) network for mRNAs interacting with these lncRNAs. It is suggested that the function of DE lncRNAs mainly correlated with transcriptional regulation demonstrated by GO analysis. Also, KEGG enrichment analysis showed these lncRNAs were involved in tumor necrosis factor, calcium, Wnt, and NF-kappa B signaling pathways. Interestingly, the PPI network revealed that a variety of transcription factors in the ceRNA network interacted with each other, suggesting such lncRNAs may regulate transcription in HD by controlling the expression of such protein-coding genes, especially transcription factors. Conclusions Our research provides new clues for uncovering the mechanism of lncRNAs in HD and can be used as the focus for further investigation.

Download Full-text

Integrated analysis of differentially expressed genes and construction of a competing endogenous RNA network in human Huntington neural progenitor cells

BMC Medical Genomics ◽

10.1186/s12920-021-00894-2 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Xiaoping Tan ◽

Yang Liu ◽

Taiming Zhang ◽

Shuyan Cong

Keyword(s):

Transcription Factors ◽

Progenitor Cells ◽

Neural Progenitor Cells ◽

Integrated Analysis ◽

Ppi Network ◽

Competing Endogenous Rna ◽

Protein Coding ◽

Protein Coding Genes ◽

Cerna Network ◽

Non Coding Rnas

Abstract Background Huntington's disease (HD) is one of the most common polyglutamine disorders, leading to progressive dyskinesia, cognitive impairment, and neuropsychological problems. Besides the dysregulation of many protein-coding genes in HD, previous studies have revealed a variety of non-coding RNAs that are also dysregulated in HD, including several long non-coding RNAs (lncRNAs). However, an integrated analysis of differentially expressed (DE) genes based on a competing endogenous RNA (ceRNA) network is still currently lacking. Methods In this study, we have systematically analyzed the gene expression profile data of neural progenitor cells (NPCs) derived from patients with HD and controls (healthy controls and the isogenic controls of HD patient cell lines corrected using a CRISPR-Cas9 approach at the HTT locus) to screen out DE mRNAs and DE lncRNAs and create a ceRNA network. To learn more about the possible functions of lncRNAs in the ceRNA regulatory network in HD, we conducted a functional analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) and established a protein–protein interaction (PPI) network for mRNAs interacting with these lncRNAs. Results We identified 490 DE mRNAs and 94 DE lncRNAs, respectively. Of these, 189 mRNAs and 20 lncRNAs were applied to create a ceRNA network. The results showed that the function of DE lncRNAs mainly correlated with transcriptional regulation as demonstrated by GO analysis. Also, KEGG enrichment analysis showed these lncRNAs were involved in tumor necrosis factor, calcium, Wnt, and NF-kappa B signaling pathways. Interestingly, the PPI network revealed that a variety of transcription factors in the ceRNA network interacted with each other, suggesting such lncRNAs may regulate transcription in HD by controlling the expression of such protein-coding genes, especially transcription factors. Conclusions Our research provides new clues for uncovering the mechanisms of lncRNAs in HD and can be used as the focus for further investigation.

Download Full-text

An integrated analysis of the competing endogenous RNA network and co-expression network revealed seven hub long non-coding RNAs in osteoarthritis

Bone and Joint Research ◽

10.1302/2046-3758.93.bjr-2019-0140.r2 ◽

2020 ◽

Vol 9 (3) ◽

pp. 90-98 ◽

Cited By ~ 1

Author(s):

Haitao Chen ◽

Liaobin Chen

Keyword(s):

Extracellular Matrix ◽

Expression Profiles ◽

Osteoclast Differentiation ◽

Signalling Pathway ◽

Differentially Expressed ◽

Integrated Analysis ◽

Knee Cartilage ◽

Competing Endogenous Rna ◽

Cerna Network ◽

Non Coding Rnas

Aims This study aimed to uncover the hub long non-coding RNAs (lncRNAs) differentially expressed in osteoarthritis (OA) cartilage using an integrated analysis of the competing endogenous RNA (ceRNA) network and co-expression network. Methods Expression profiles data of ten OA and ten normal tissues of human knee cartilage were obtained from the Gene Expression Omnibus (GEO) database (GSE114007). The differentially expressed messenger RNAs (DEmRNAs) and lncRNAs (DElncRNAs) were identified using the edgeR package. We integrated human microRNA (miRNA)-lncRNA/mRNA interactions with DElncRNA/DEmRNA expression profiles to construct a ceRNA network. Likewise, lncRNA and mRNA expression profiles were used to build a co-expression network with the WGCNA package. Potential hub lncRNAs were identified based on an integrated analysis of the ceRNA network and co-expression network. StarBase and Multi Experiment Matrix databases were used to verify the lncRNAs. Results We detected 1,212 DEmRNAs and 49 DElncRNAs in OA and normal knee cartilage. A total of 75 dysregulated lncRNA-miRNA interactions and 711 dysregulated miRNA-mRNA interactions were obtained in the ceRNA network, including ten DElncRNAs, 69 miRNAs, and 72 DEmRNAs. Similarly, 1,330 dysregulated lncRNA-mRNA interactions were used to construct the co-expression network, which included ten lncRNAs and 407 mRNAs. We finally identified seven hub lncRNAs, named MIR210HG, HCP5, LINC00313, LINC00654, LINC00839, TBC1D3P1-DHX40P1, and ISM1-AS1. Subsequent enrichment analysis elucidated that these lncRNAs regulated extracellular matrix organization and enriched in osteoclast differentiation, the FoxO signalling pathway, and the tumour necrosis factor (TNF) signalling pathway in the development of OA. Conclusion The integrated analysis of the ceRNA network and co-expression network identified seven hub lncRNAs associated with OA. These lncRNAs may regulate extracellular matrix changes and chondrocyte homeostasis in OA progress. Cite this article: Bone Joint Res. 2020;9(3):90–98.

Download Full-text

Functional and transcriptional profiling of non-coding RNAs in yeast reveal context-dependent phenotypes and widespread in trans effects on the protein regulatory network

10.1101/2020.04.07.029611 ◽

2020 ◽

Author(s):

Laura Natalia Balarezo-Cisneros ◽

Steven Parker ◽

Marcin G Fraczek ◽

Soukaina Timouma ◽

Ping Wang ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Environmental Conditions ◽

Mode Of Action ◽

Protein Coding ◽

Protein Coding Genes ◽

Genome Wide ◽

In Trans ◽

Non Coding Rnas ◽

The Impact

AbstractNon-coding RNAs (ncRNAs), including the more recently identified Stable Unannotated Transcripts (SUTs) and Cryptic Unstable Transcripts (CUTs), are increasingly being shown to play pivotal roles in the transcriptional and post-transcriptional regulation of genes in eukaryotes. Here, we carried out a large-scale screening of ncRNAs in Saccharomyces cerevisiae, and provide evidence for SUT and CUT function. Phenotypic data on 372 ncRNA deletion strains in 23 different growth conditions were collected, identifying ncRNAs responsible for significant cellular fitness changes. Transcriptome profiles were assembled for 18 haploid ncRNA deletion mutants and 2 essential ncRNA heterozygous deletants. Guided by the resulting RNA-seq data we analysed the genome-wide dysregulation of protein coding genes and non-coding transcripts. Novel functional ncRNAs, SUT125, SUT126, SUT035 and SUT532 that act in trans by modulating transcription factors were identified. Furthermore, we described the impact of SUTs and CUTs in modulating coding gene expression in response of different environmental conditions, regulating important biological process such as respiration (SUT125, SUT126, SUT035, SUT432), steroid biosynthesis (CUT494, SUT530, SUT468) or rRNA processing (SUT075 and snR30). Overall, this data captures and integrates the regulatory and phenotypic network of ncRNAs and protein coding genes, providing genome-wide evidence of the impact of ncRNAs on cellular homeostasis.Author SummaryThe yeast genome contains 25% of non-coding RNA molecules (ncRNAs), which do not translate into proteins but are involved in regulation of gene expression. ncRNAs can affect nearby genes by physically interfering with their transcription (cis mode of action), or they interact with DNA, proteins or others RNAs to regulate the expression of distant genes (trans mode of action). Examples of cis-acting ncRNAs have been broadly described, however genome-wide studies to identify functional trans-acting ncRNAs involved in global gene regulation are still lacking. Here, we used the ncRNA yeast deletion collection to score their impact on cellular function in different environmental conditions. A group of 20 ncRNAs mutants with broad fitness diversity were selected to investigate their effect on the protein and ncRNA expression network. We showed a high correlation between altered phenotypes and global transcriptional changes, in an environmental dependent manner. We confirmed the widespread trans acting expressional regulation of ncRNAs in the genome and their role in affecting transcription factors. These findings support the notion of the involvement on ncRNAs in fine tuning the cellular expression via regulations of TFs, as an advantageous RNA-mediated mechanism that can be fast and cost-effective for the cells.

Download Full-text

An integrative atlas of chicken long non-coding genes and their annotations across 25 tissues

Scientific Reports ◽

10.1038/s41598-020-77586-x ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Frédéric Jehl ◽

Kévin Muret ◽

Maria Bernard ◽

Morgane Boutin ◽

Laetitia Lagoutte ◽

...

Keyword(s):

Transcription Factors ◽

Biological Processes ◽

Rna Seq ◽

Protein Coding ◽

Tissue Specific ◽

Protein Coding Genes ◽

Intergenic Regions ◽

Immune Tissues ◽

Non Coding Rnas

AbstractLong non-coding RNAs (LNC) regulate numerous biological processes. In contrast to human, the identification of LNC in farm species, like chicken, is still lacunar. We propose a catalogue of 52,075 chicken genes enriched in LNC (http://www.fragencode.org/), built from the Ensembl reference extended using novel LNC modelled here from 364 RNA-seq and LNC from four public databases. The Ensembl reference grew from 4,643 to 30,084 LNC, of which 59% and 41% with expression ≥ 0.5 and ≥ 1 TPM respectively. Characterization of these LNC relatively to the closest protein coding genes (PCG) revealed that 79% of LNC are in intergenic regions, as in other species. Expression analysis across 25 tissues revealed an enrichment of co-expressed LNC:PCG pairs, suggesting co-regulation and/or co-function. As expected LNC were more tissue-specific than PCG (25% vs. 10%). Similarly to human, 16% of chicken LNC hosted one or more miRNA. We highlighted a new chicken LNC, hosting miR155, conserved in human, highly expressed in immune tissues like miR155, and correlated with immunity-related PCG in both species. Among LNC:PCG pairs tissue-specific in the same tissue, we revealed an enrichment of divergent pairs with the PCG coding transcription factors, as for example LHX5, HXD3 and TBX4, in both human and chicken.

Download Full-text

Integrated analysis of long non-coding RNAs and mRNAs reveals the regulatory network of maize seedling root responding to salt stress

BMC Genomics ◽

10.1186/s12864-021-08286-7 ◽

2022 ◽

Vol 23 (1) ◽

Author(s):

Peng Liu ◽

Yinchao Zhang ◽

Chaoying Zou ◽

Cong Yang ◽

Guangtang Pan ◽

...

Keyword(s):

Salt Stress ◽

Salt Tolerance ◽

Inbred Lines ◽

Maize Seedling ◽

Integrated Analysis ◽

Regulatory Pathway ◽

Protein Coding ◽

Protein Coding Genes ◽

Non Coding Rnas ◽

Whole Transcriptome

Abstract Background Long non-coding RNAs (lncRNAs) play important roles in response to abiotic stresses in plants, by acting as cis- or trans-acting regulators of protein-coding genes. As a widely cultivated crop worldwide, maize is sensitive to salt stress particularly at the seedling stage. However, it is unclear how the expressions of protein-coding genes are affected by non-coding RNAs in maize responding to salt tolerance. Results The whole transcriptome sequencing was employed to investigate the differential lncRNAs and target transcripts responding to salt stress between two maize inbred lines with contrasting salt tolerance. We developed a flexible, user-friendly, and modular RNA analysis workflow, which facilitated the identification of lncRNAs and novel mRNAs from whole transcriptome data. Using the workflow, 12,817 lncRNAs and 8,320 novel mRNAs in maize seedling roots were identified and characterized. A total of 742 lncRNAs and 7,835 mRNAs were identified as salt stress-responsive transcripts. Moreover, we obtained 41 cis- and 81 trans-target mRNA for 88 of the lncRNAs. Among these target transcripts, 11 belonged to 7 transcription factor (TF) families including bHLH, C2H2, Hap3/NF-YB, HAS, MYB, WD40, and WRKY. The above 8,577 salt stress-responsive transcripts were further classified into 28 modules by weighted gene co-expression network analysis. In the salt-tolerant module, we constructed an interaction network containing 79 nodes and 3081 edges, which included 5 lncRNAs, 18 TFs and 56 functional transcripts (FTs). As a trans-acting regulator, the lncRNA MSTRG.8888.1 affected the expressions of some salt tolerance-relative FTs, including protein-serine/threonine phosphatase 2C and galactinol synthase 1, by regulating the expression of the bHLH TF. Conclusions The contrasting genetic backgrounds of the two inbred lines generated considerable variations in the expression abundance of lncRNAs and protein-coding transcripts. In the co-expression networks responding to salt stress, some TFs were targeted by the lncRNAs, which further regulated the salt tolerance-related functional transcripts. We constructed a regulatory pathway of maize seedlings to salt stress, which was mediated by the hub lncRNA MSTRG.8888.1 and participated by the bHLH TF and its downstream target transcripts. Future work will be focused on the functional revelation of the regulatory pathway.

Download Full-text