E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Special Issue "Transcriptome Profiling in Human Diseases"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (30 June 2017)

Special Issue Editor

Guest Editor
Prof. Dr. Alfredo Ciccodicola

CNR, Institute of Genetics and Biophysics “Adriano Buzzati-Traverso”, Via Pietro Castellino 111-80131, Naples, Italy; Department of Science and Technology, University of Naples “Parthenope", Centro Direzionale, Isola C4-800143, Naples, Italy
E-Mail
Interests: human genetic diseases; molecular mechanism pathogenesis; whole-transcriptome analysis; non-coding RNAs

Special Issue Information

Dear Colleagues,

In recent years, whole-transcriptome analysis with total RNA sequencing (RNA-Seq) has emerged as the gold standard for quantifying gene expression levels and allele-specific expression in a single experiment, as well as to identify novel genes, splice isoforms, chimeric transcripts, and to investigate non-coding RNAs. RNA-Seq also provides an important technique, often used in studies of human disease. A great of emphasis has been given to RNA-Seq data with the ENCODE (Encyclopedia of the regulatory elements) and TCGA (The Cancer Genome Atlas) projects that deployed this direct technique to characterize dozens of cell lines and thousands of primary tumor specimens, respectively. In this scenario, RNA-Seq data provide a unique snapshot of the transcriptomic level of the human disease and show at an unbiased proportion of transcripts that allows the identification of novel transcripts, fusion transcripts, and non-coding RNAs that could be remain undetected with other different technologies.

This Special Issue, “Transcriptome Profiling in Human Diseases”, will cover a selection of recent research topics and current review articles in the field of human complex and Mendelian disorders that have been analyzed by the RNA-Seq technique. Experimental and Bioinformatics papers, up-to-date review articles, and commentaries are also welcome.

Prof. Dr. Alfredo Ciccodicola
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • whole-transcriptome analysis
  • RNA sequencing
  • human complex diseases
  • Mendelian disorders
  • allele-specific expression
  • novel transcripts
  • new splice isoforms
  • chimeric transcripts
  • non-coding RNAs

Published Papers (12 papers)

View options order results:
result details:
Displaying articles 1-12
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle
Pan-Cancer Mutational and Transcriptional Analysis of the Integrator Complex
Int. J. Mol. Sci. 2017, 18(5), 936; https://doi.org/10.3390/ijms18050936
Received: 10 April 2017 / Revised: 20 April 2017 / Accepted: 23 April 2017 / Published: 29 April 2017
Cited by 6 | PDF Full-text (4074 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The integrator complex has been recently identified as a key regulator of RNA Polymerase II-mediated transcription, with many functions including the processing of small nuclear RNAs, the pause-release and elongation of polymerase during the transcription of protein coding genes, and the biogenesis of [...] Read more.
The integrator complex has been recently identified as a key regulator of RNA Polymerase II-mediated transcription, with many functions including the processing of small nuclear RNAs, the pause-release and elongation of polymerase during the transcription of protein coding genes, and the biogenesis of enhancer derived transcripts. Moreover, some of its components also play a role in genome maintenance. Thus, it is reasonable to hypothesize that their functional impairment or altered expression can contribute to malignancies. Indeed, several studies have described the mutations or transcriptional alteration of some Integrator genes in different cancers. Here, to draw a comprehensive pan-cancer picture of the genomic and transcriptomic alterations for the members of the complex, we reanalyzed public data from The Cancer Genome Atlas. Somatic mutations affecting Integrator subunit genes and their transcriptional profiles have been investigated in about 11,000 patients and 31 tumor types. A general heterogeneity in the mutation frequencies was observed, mostly depending on tumor type. Despite the fact that we could not establish them as cancer drivers, INTS7 and INTS8 genes were highly mutated in specific cancers. A transcriptome analysis of paired (normal and tumor) samples revealed that the transcription of INTS7, INTS8, and INTS13 is significantly altered in several cancers. Experimental validation performed on primary tumors confirmed these findings. Full article
(This article belongs to the Special Issue Transcriptome Profiling in Human Diseases)
Figures

Graphical abstract

Open AccessArticle
Genome-Wide Analyses of MicroRNA Profiling in Interleukin-27 Treated Monocyte-Derived Human Dendritic Cells Using Deep Sequencing: A Pilot Study
Int. J. Mol. Sci. 2017, 18(5), 925; https://doi.org/10.3390/ijms18050925
Received: 25 January 2017 / Revised: 20 April 2017 / Accepted: 25 April 2017 / Published: 28 April 2017
Cited by 4 | PDF Full-text (1146 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
MicroRNAs (miRNAs) regulate gene expression and thereby influence cell fate and function. Recent studies suggest that an abundant class of miRNAs play important roles in immune cells, such as T cells, natural killer (NK) cells, B cells, and dendritic cells (DCs). Interleukin (IL)-27 [...] Read more.
MicroRNAs (miRNAs) regulate gene expression and thereby influence cell fate and function. Recent studies suggest that an abundant class of miRNAs play important roles in immune cells, such as T cells, natural killer (NK) cells, B cells, and dendritic cells (DCs). Interleukin (IL)-27 is a member of the IL-12 family of cytokines with broad anti-viral effects. It is a potent inhibitor of HIV-1 infection in CD4+ T cells and macrophages, as well as monocyte-derived immature dendritic cells (iDCs). This pilot study compared miRNA profiles between iDCs and IL-27-treated iDCs (27DCs) using deep sequencing methods and identified 46 known miRNAs that were significantly differentially expressed in 27DCs: 36 were upregulated and 10 downregulated by IL-27. Many of the potential target genes of these miRNAs are involved in IL-27 associated pathways, such as JAK/STAT, MAPKs, and PI3K and several were also previously reported to be involved in the regulation of human DC function. This study found that these miRNAs also potentially target several viral genomes and therefore may have antiviral effects. Four of these differential miRNAs (miR-99a-5p, miR-222-3p, miR-138-5p, and miR-125b-5p) were validated using quantitative reverse transcription PCR (RT-qPCR). Twenty-two novel miRNAs were discovered from deep sequencing and confirmed using RT-qPCR. This study furthers the understanding of the role of IL-27 in immunity and lays a foundation for future characterization of the role of specific miRNAs in DCs. Full article
(This article belongs to the Special Issue Transcriptome Profiling in Human Diseases)
Figures

Graphical abstract

Open AccessArticle
Distinct Antigen Delivery Systems Induce Dendritic Cells’ Divergent Transcriptional Response: New Insights from a Comparative and Reproducible Computational Analysis
Int. J. Mol. Sci. 2017, 18(3), 494; https://doi.org/10.3390/ijms18030494
Received: 5 January 2017 / Revised: 11 February 2017 / Accepted: 21 February 2017 / Published: 25 February 2017
Cited by 3 | PDF Full-text (2552 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Vaccination is the most successful and cost-effective method to prevent infectious diseases. However, many vaccine antigens have poor in vivo immunogenic potential and need adjuvants to enhance immune response. The application of systems biology to immunity and vaccinology has yielded crucial insights about [...] Read more.
Vaccination is the most successful and cost-effective method to prevent infectious diseases. However, many vaccine antigens have poor in vivo immunogenic potential and need adjuvants to enhance immune response. The application of systems biology to immunity and vaccinology has yielded crucial insights about how vaccines and adjuvants work. We have previously characterized two safe and powerful delivery systems derived from non-pathogenic prokaryotic organisms: E2 and fd filamentous bacteriophage systems. They elicit an in vivo immune response inducing CD8+ T-cell responses, even in absence of adjuvants or stimuli for dendritic cells’ maturation. Nonetheless, a systematic and comparative analysis of the complex gene expression network underlying such activation is missing. Therefore, we compared the transcriptomes of ex vivo isolated bone marrow-derived dendritic cells exposed to these antigen delivery systems. Significant differences emerged, especially for genes involved in innate immunity, co-stimulation, and cytokine production. Results indicate that E2 drives polarization toward the Th2 phenotype, mainly mediated by Irf4, Ccl17, and Ccr4 over-expression. Conversely, fd-scαDEC-205 triggers Th1 T cells’ polarization through the induction of Il12b, Il12rb, Il6, and other molecules involved in its signal transduction. The data analysis was performed using RNASeqGUI, hence, addressing the increasing need of transparency and reproducibility of computational analysis. Full article
(This article belongs to the Special Issue Transcriptome Profiling in Human Diseases)
Figures

Graphical abstract

Open AccessArticle
Analysis of Epidermal Growth Factor Receptor Related Gene Expression Changes in a Cellular and Animal Model of Parkinson’s Disease
Int. J. Mol. Sci. 2017, 18(2), 430; https://doi.org/10.3390/ijms18020430
Received: 24 October 2016 / Revised: 27 January 2017 / Accepted: 8 February 2017 / Published: 16 February 2017
Cited by 1 | PDF Full-text (1723 KB) | HTML Full-text | XML Full-text
Abstract
We employed transcriptome analysis of epidermal growth factor receptor related gene expression changes in cellular and animal models of Parkinson’s disease (PD). We used a well-known Parkinsonian toxin 1-methyl-4-phenylpyridine (MPP+) to induce neuronal apoptosis in the human neuroblastoma SH-SY5Y cell line. [...] Read more.
We employed transcriptome analysis of epidermal growth factor receptor related gene expression changes in cellular and animal models of Parkinson’s disease (PD). We used a well-known Parkinsonian toxin 1-methyl-4-phenylpyridine (MPP+) to induce neuronal apoptosis in the human neuroblastoma SH-SY5Y cell line. The MPP+-treatment of SH-SY5Y cells was capable of inducing neuro-apoptosis, but it remains unclear what kinds of transcriptional genes are affected by MPP+ toxicity. Therefore the pathways that were significantly perturbed in MPP+ treated human neuroblastoma SH-SY5Y cells were identified based on genome-wide gene expression data at two time points (24 and 48 h). We found that the Epidermal Growth Factor Receptor (EGFR) pathway-related genes showed significantly differential expression at all time points. The EGFR pathway has been linked to diverse cellular events such as proliferation, differentiation, and apoptosis. Further, to evaluate the functional significance of the altered EGFR related gene expression observed in MPP+-treated SH-SY5Y cells, the EGFR related GJB2 (Cx26) gene expression was analyzed in an MPP+-intoxicated animal PD model. Our findings identify that the EGFR signaling pathway and its related genes, such as Cx26, might play a significant role in dopaminergic (DAergic) neuronal cell death during the process of neuro-apoptosis and therefore can be focused on as potential targets for therapeutic intervention. Full article
(This article belongs to the Special Issue Transcriptome Profiling in Human Diseases)
Figures

Graphical abstract

Open AccessArticle
SpidermiR: An R/Bioconductor Package for Integrative Analysis with miRNA Data
Int. J. Mol. Sci. 2017, 18(2), 274; https://doi.org/10.3390/ijms18020274
Received: 1 December 2016 / Revised: 23 January 2017 / Accepted: 24 January 2017 / Published: 27 January 2017
Cited by 12 | PDF Full-text (1139 KB) | HTML Full-text | XML Full-text
Abstract
Gene Regulatory Networks (GRNs) control many biological systems, but how such network coordination is shaped is still unknown. GRNs can be subdivided into basic connections that describe how the network members interact e.g., co-expression, physical interaction, co-localization, genetic influence, pathways, and shared protein [...] Read more.
Gene Regulatory Networks (GRNs) control many biological systems, but how such network coordination is shaped is still unknown. GRNs can be subdivided into basic connections that describe how the network members interact e.g., co-expression, physical interaction, co-localization, genetic influence, pathways, and shared protein domains. The important regulatory mechanisms of these networks involve miRNAs. We developed an R/Bioconductor package, namely SpidermiR, which offers an easy access to both GRNs and miRNAs to the end user, and integrates this information with differentially expressed genes obtained from The Cancer Genome Atlas. Specifically, SpidermiR allows the users to: (i) query and download GRNs and miRNAs from validated and predicted repositories; (ii) integrate miRNAs with GRNs in order to obtain miRNA–gene–gene and miRNA–protein–protein interactions, and to analyze miRNA GRNs in order to identify miRNA–gene communities; and (iii) graphically visualize the results of the analyses. These analyses can be performed through a single interface and without the need for any downloads. The full data sets are then rapidly integrated and processed locally. Full article
(This article belongs to the Special Issue Transcriptome Profiling in Human Diseases)
Figures

Graphical abstract

Open AccessArticle
Anti-NMDA Receptor Encephalitis and Vaccination
Int. J. Mol. Sci. 2017, 18(1), 193; https://doi.org/10.3390/ijms18010193
Received: 15 October 2016 / Revised: 10 January 2017 / Accepted: 13 January 2017 / Published: 18 January 2017
Cited by 6 | PDF Full-text (903 KB) | HTML Full-text | XML Full-text
Abstract
Anti-N-methyl-d-aspartate (Anti-NMDA) receptor encephalitis is an acute autoimmune neurological disorder. The cause of this disease is often unknown, and previous studies revealed that it might be caused by a virus, vaccine or tumor. It occurs more often in females [...] Read more.
Anti-N-methyl-d-aspartate (Anti-NMDA) receptor encephalitis is an acute autoimmune neurological disorder. The cause of this disease is often unknown, and previous studies revealed that it might be caused by a virus, vaccine or tumor. It occurs more often in females than in males. Several cases were reported to be related to vaccination such as the H1N1 vaccine and tetanus/diphtheria/pertussis and polio vaccines. In this study, we reported an anti-NMDA receptor encephalitis case that may be caused by Japanese encephalitis vaccination. To investigate the association between anti-NMDA receptor encephalitis and vaccination, we analyzed the phylogenetic relationship of the microRNAs, which significantly regulate these vaccine viruses or bacteria, and the phylogenetic relationship of these viruses and bacteria. This reveals that anti-NMDA receptor encephalitis may be caused by Japanese encephalitis vaccination, as well as H1N1 vaccination or tetanus/diphtheria/pertussis and polio vaccinations, from the phylogenetic viewpoint. Full article
(This article belongs to the Special Issue Transcriptome Profiling in Human Diseases)
Figures

Graphical abstract

Open AccessArticle
Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways
Int. J. Mol. Sci. 2016, 17(12), 2091; https://doi.org/10.3390/ijms17122091
Received: 25 September 2016 / Revised: 2 December 2016 / Accepted: 5 December 2016 / Published: 13 December 2016
Cited by 8 | PDF Full-text (791 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Heritable profibrotic differentiation of lung fibroblasts is a key mechanism of idiopathic pulmonary fibrosis (IPF). Its mechanisms are yet to be fully understood. In this study, individual data from four independent microarray studies comparing the transcriptome of fibroblasts cultured in vitro from normal [...] Read more.
Heritable profibrotic differentiation of lung fibroblasts is a key mechanism of idiopathic pulmonary fibrosis (IPF). Its mechanisms are yet to be fully understood. In this study, individual data from four independent microarray studies comparing the transcriptome of fibroblasts cultured in vitro from normal (total n = 20) and IPF (total n = 20) human lung were compiled for meta-analysis following normalization to z-scores. One hundred and thirteen transcripts were upregulated and 115 were downregulated in IPF fibroblasts using the Significance Analysis of Microrrays algorithm with a false discovery rate of 5%. Downregulated genes were highly enriched for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional classes related to inflammation and immunity such as Defense response to virus, Influenza A, tumor necrosis factor (TNF) mediated signaling pathway, interferon-inducible absent in melanoma2 (AIM2) inflammasome as well as Apoptosis. Although upregulated genes were not enriched for any functional class, select factors known to play key roles in lung fibrogenesis were overexpressed in IPF fibroblasts, most notably connective tissue growth factor (CTGF) and serum response factor (SRF), supporting their role as drivers of IPF. The full data table is available as a supplement. Full article
(This article belongs to the Special Issue Transcriptome Profiling in Human Diseases)
Figures

Figure 1

Open AccessArticle
Transcriptomic Insights into the Response of Placenta and Decidua Basalis to the CpG Oligodeoxynucleotide Stimulation in Non-Obese Diabetic Mice and Wild-Type Controls
Int. J. Mol. Sci. 2016, 17(8), 1281; https://doi.org/10.3390/ijms17081281
Received: 21 June 2016 / Revised: 26 July 2016 / Accepted: 28 July 2016 / Published: 5 August 2016
PDF Full-text (4127 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Intrauterine infection is one of the most frequent causes of miscarriage. CpG oligodeoxynucleotide (CpG ODN) can mimic intrauterine infection. CpG ODN-induced embryo-resorption was observed consistently in the NK-cell deficient non-obese diabetic (NOD) mice but not in the wild-type (WT) mice. To elucidate the [...] Read more.
Intrauterine infection is one of the most frequent causes of miscarriage. CpG oligodeoxynucleotide (CpG ODN) can mimic intrauterine infection. CpG ODN-induced embryo-resorption was observed consistently in the NK-cell deficient non-obese diabetic (NOD) mice but not in the wild-type (WT) mice. To elucidate the molecular mechanisms of differential pregnancy outcomes, differentially expressed genes (DEGs) in the placenta and decidua basalis was revealed by RNA-Seq with CpG ODN or control ODN treatment. Common DEGs in the WT and NOD mice were enriched in antimicrobial/antibacterial humoral responses that may be activated as a primary response to bacterial infection. The susceptibility to CpG ODN-induced embryo-resorption in the NOD mice might mainly be attributed to M1 macrophage polarization and the immunodeficient status, such as the down-regulation in antigen processing and presentation, allograft rejection, and natural killer cell mediated cytotoxicity. In contrast, the WT mice with normal immune systems could activate multiple immune responses and be resistant to CpG ODN-induced embryo-resorption, such as M2 macrophage differentiation and activation regulated by complement component C1q and peroxisome proliferation-activated receptor (PPAR) signaling pathways. Collectively, this study suggests that the immunodeficient status of NOD mice and the macrophage polarization regulated by C1q and PPAR signaling might be the basis for differential pregnancy outcomes between the NOD and WT mice. Full article
(This article belongs to the Special Issue Transcriptome Profiling in Human Diseases)
Figures

Graphical abstract

Open AccessArticle
Correlation between Gene Expression and Osteoarthritis Progression in Human
Int. J. Mol. Sci. 2016, 17(7), 1126; https://doi.org/10.3390/ijms17071126
Received: 17 June 2016 / Revised: 8 July 2016 / Accepted: 11 July 2016 / Published: 14 July 2016
Cited by 21 | PDF Full-text (5805 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Osteoarthritis (OA) is a multifactorial disease characterized by gradual degradation of joint cartilage. This study aimed to quantify major pathogenetic factors during OA progression in human cartilage. Cartilage specimens were isolated from OA patients and scored 0–5 according to the Osteoarthritis Research Society [...] Read more.
Osteoarthritis (OA) is a multifactorial disease characterized by gradual degradation of joint cartilage. This study aimed to quantify major pathogenetic factors during OA progression in human cartilage. Cartilage specimens were isolated from OA patients and scored 0–5 according to the Osteoarthritis Research Society International (OARSI) guidelines. Protein and gene expressions were measured by immunohistochemistry and qPCR, respectively. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were used to detect apoptotic cells. Cartilage degeneration in OA is a gradual progress accompanied with gradual loss of collagen type II and a gradual decrease in mRNA expression of SOX9, ACAN and COL2A1. Expression of WNT antagonists DKK1 and FRZB was lost, while hypertrophic markers (RUNX2, COL10A1 and IHH) increased during OA progression. Moreover, DKK1 and FRZB negatively correlated with OA grading, while RUNX2 and IHH showed a significantly positive correlation with OA grading. The number of apoptotic cells was increased with the severity of OA. Taken together, our results suggested that genetic profiling of the gene expression could be used as markers for staging OA at the molecular level. This helps to understand the molecular pathology of OA and may lead to the development of therapies based on OA stage. Full article
(This article belongs to the Special Issue Transcriptome Profiling in Human Diseases)
Figures

Figure 1

Review

Jump to: Research

Open AccessReview
Transcriptome Profiling in Human Diseases: New Advances and Perspectives
Int. J. Mol. Sci. 2017, 18(8), 1652; https://doi.org/10.3390/ijms18081652
Received: 30 June 2017 / Revised: 21 July 2017 / Accepted: 27 July 2017 / Published: 29 July 2017
Cited by 18 | PDF Full-text (659 KB) | HTML Full-text | XML Full-text
Abstract
In the last decades, transcriptome profiling has been one of the most utilized approaches to investigate human diseases at the molecular level. Through expression studies, many molecular biomarkers and therapeutic targets have been found for several human pathologies. This number is continuously increasing [...] Read more.
In the last decades, transcriptome profiling has been one of the most utilized approaches to investigate human diseases at the molecular level. Through expression studies, many molecular biomarkers and therapeutic targets have been found for several human pathologies. This number is continuously increasing thanks to total RNA sequencing. Indeed, this new technology has completely revolutionized transcriptome analysis allowing the quantification of gene expression levels and allele-specific expression in a single experiment, as well as to identify novel genes, splice isoforms, fusion transcripts, and to investigate the world of non-coding RNA at an unprecedented level. RNA sequencing has also been employed in important projects, like ENCODE (Encyclopedia of the regulatory elements) and TCGA (The Cancer Genome Atlas), to provide a snapshot of the transcriptome of dozens of cell lines and thousands of primary tumor specimens. Moreover, these studies have also paved the way to the development of data integration approaches in order to facilitate management and analysis of data and to identify novel disease markers and molecular targets to use in the clinics. In this scenario, several ongoing clinical trials utilize transcriptome profiling through RNA sequencing strategies as an important instrument in the diagnosis of numerous human pathologies. Full article
(This article belongs to the Special Issue Transcriptome Profiling in Human Diseases)
Figures

Graphical abstract

Open AccessReview
lncRNAs and MYC: An Intricate Relationship
Int. J. Mol. Sci. 2017, 18(7), 1497; https://doi.org/10.3390/ijms18071497
Received: 21 June 2017 / Revised: 5 July 2017 / Accepted: 11 July 2017 / Published: 12 July 2017
Cited by 6 | PDF Full-text (555 KB) | HTML Full-text | XML Full-text
Abstract
Long non-coding RNAs (lncRNAs) are emerging as important regulators of gene expression networks, acting either at the transcriptional level, by influencing histone modifications, or at the post-transcriptional level, by controlling mRNA stability and translation. Among the gene expression networks known to influence the [...] Read more.
Long non-coding RNAs (lncRNAs) are emerging as important regulators of gene expression networks, acting either at the transcriptional level, by influencing histone modifications, or at the post-transcriptional level, by controlling mRNA stability and translation. Among the gene expression networks known to influence the process of oncogenic transformation, the one controlled by the proto-oncogene MYC is one of the most frequently deregulated in cancer. In B-cell lymphomas, the MYC gene is subject to chromosomal rearrangements that result in MYC overexpression. In many other cancers, the region surrounding MYC is subject to gene amplification. MYC expression is also controlled at the level of protein and mRNA stability. Neoplastic lesions affecting MYC expression are responsible for a drastic change in the number and the type of genes that are transcriptionally controlled by MYC, depending on differential promoter affinities. Transcriptome profiling of tumor samples has shown that several lncRNAs can be found differentially regulated by MYC in different cancer types and many of them can influence cancer cell viability and proliferation. At the same time, lncRNAs have been shown to be able to control the expression of MYC itself, both at transcriptional and post-transcriptional levels. Given that targeting the MYC-dependent transcriptional program has the potential to reach broad anticancer activity, molecular dissection of the complex regulatory mechanisms governing MYC expression will be crucial in the future for the identification of novel therapeutic strategies. Full article
(This article belongs to the Special Issue Transcriptome Profiling in Human Diseases)
Figures

Figure 1

Open AccessReview
Transcriptomics, NF-κB Pathway, and Their Potential Spaceflight-Related Health Consequences
Int. J. Mol. Sci. 2017, 18(6), 1166; https://doi.org/10.3390/ijms18061166
Received: 1 March 2017 / Revised: 22 May 2017 / Accepted: 23 May 2017 / Published: 31 May 2017
Cited by 8 | PDF Full-text (845 KB) | HTML Full-text | XML Full-text
Abstract
In space, living organisms are exposed to multiple stress factors including microgravity and space radiation. For humans, these harmful environmental factors have been known to cause negative health impacts such as bone loss and immune dysfunction. Understanding the mechanisms by which spaceflight impacts [...] Read more.
In space, living organisms are exposed to multiple stress factors including microgravity and space radiation. For humans, these harmful environmental factors have been known to cause negative health impacts such as bone loss and immune dysfunction. Understanding the mechanisms by which spaceflight impacts human health at the molecular level is critical not only for accurately assessing the risks associated with spaceflight, but also for developing effective countermeasures. Over the years, a number of studies have been conducted under real or simulated space conditions. RNA and protein levels in cellular and animal models have been targeted in order to identify pathways affected by spaceflight. Of the many pathways responsive to the space environment, the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) network appears to commonly be affected across many different cell types under the true or simulated spaceflight conditions. NF-κB is of particular interest, as it is associated with many of the spaceflight-related health consequences. This review intends to summarize the transcriptomics studies that identified NF-κB as a responsive pathway to ground-based simulated microgravity or the true spaceflight condition. These studies were carried out using either human cell or animal models. In addition, the review summarizes the studies that focused specifically on NF-κB pathway in specific cell types or organ tissues as related to the known spaceflight-related health risks including immune dysfunction, bone loss, muscle atrophy, central nerve system (CNS) dysfunction, and risks associated with space radiation. Whether the NF-κB pathway is activated or inhibited in space is dependent on the cell type, but the potential health impact appeared to be always negative. It is argued that more studies on NF-κB should be conducted to fully understand this particular pathway for the benefit of crew health in space. Full article
(This article belongs to the Special Issue Transcriptome Profiling in Human Diseases)
Figures

Figure 1

Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top