scholarly journals When Viruses Cross Developmental Pathways

2021 ◽  
Vol 9 ◽  
Author(s):  
Pankaj Trivedi ◽  
Sandesh Kumar Patel ◽  
Diana Bellavia ◽  
Elena Messina ◽  
Rocco Palermo ◽  
...  
Keyword(s):  
Human Tumor ◽  
Lytic Cycle ◽  
Developmental Pathways ◽  
Oncogenic Viruses ◽  
Regulatory Pathways ◽  
Antiviral Therapies ◽  
Viral Immune Evasion ◽  
Tumor Viruses ◽  
Metastatic Behavior ◽  
Gene Regulatory

Aberrant regulation of developmental pathways plays a key role in tumorigenesis. Tumor cells differ from normal cells in their sustained proliferation, replicative immortality, resistance to cell death and growth inhibition, angiogenesis, and metastatic behavior. Often they acquire these features as a consequence of dysregulated Hedgehog, Notch, or WNT signaling pathways. Human tumor viruses affect the cancer cell hallmarks by encoding oncogenic proteins, and/or by modifying the microenvironment, as well as by conveying genomic instability to accelerate cancer development. In addition, viral immune evasion mechanisms may compromise developmental pathways to accelerate tumor growth. Viruses achieve this by influencing both coding and non-coding gene regulatory pathways. Elucidating how oncogenic viruses intersect with and modulate developmental pathways is crucial to understanding viral tumorigenesis. Many currently available antiviral therapies target viral lytic cycle replication but with low efficacy and severe side effects. A greater understanding of the cross-signaling between oncogenic viruses and developmental pathways will improve the efficacy of next-generation inhibitors and pave the way to more targeted antiviral therapies.

scholarly journals Virus-Driven Carcinogenesis

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2625
Author(s):  
Yuichiro Hatano ◽  
Takayasu Ideta ◽  
Akihiro Hirata ◽  
Kayoko Hatano ◽  
Hiroyuki Tomita ◽  
...  
Keyword(s):  
Insertional Mutagenesis ◽  
Human Herpesvirus ◽  
Kaposi Sarcoma ◽  
Malignant Cell ◽  
Precision Oncology ◽  
Oncogenic Viruses ◽  
Barr Virus ◽  
Human T Cell ◽  
Tumor Viruses ◽  
Tumor Virus

Cancer arises from the accumulation of genetic and epigenetic alterations. Even in the era of precision oncology, carcinogens contributing to neoplastic process are still an important focus of research. Comprehensive genomic analyses have revealed various combinations of base substitutions, referred to as the mutational signatures, in cancer. Each mutational signature is believed to arise from specific DNA damage and repair processes, including carcinogens. However, as a type of carcinogen, tumor viruses increase the cancer risk by alternative mechanisms, including insertional mutagenesis, viral oncogenes, and immunosuppression. In this review, we summarize virus-driven carcinogenesis to provide a framework for the control of malignant cell proliferation. We first provide a brief overview of oncogenic viruses and describe their implication in virus-related tumors. Next, we describe tumor viruses (HPV, Human papilloma virus; HBV, Hepatitis B virus; HCV, Hepatitis C virus; EBV, Epstein–Barr virus; Kaposi sarcoma herpesvirus; MCV, Merkel cell polyoma virus; HTLV-1, Human T-cell lymphotropic virus, type-1) and tumor virus-related cancers. Lastly, we introduce emerging tumor virus candidates, human cytomegalovirus (CMV), human herpesvirus-6 (HHV-6) and adeno-associated virus-2 (AAV-2). We expect this review to be a hub in a complex network of data for virus-associated carcinogenesis.

scholarly journals Differential gene regulatory pathways and co-expression networks associated with fire blight infection in apple (Malus × domestica)

2019 ◽  
Vol 6 (1) ◽  
Author(s):  
Katchen Julliany Pereira Silva ◽  
Jugpreet Singh ◽  
Ryland Bednarek ◽  
Zhangjun Fei ◽  
Awais Khan
Keyword(s):  
Malus Domestica ◽  
Fire Blight ◽  
Regulatory Pathways ◽  
Differential Gene ◽  
Gene Regulatory

scholarly journals Synaptic and Gene Regulatory Mechanisms in Schizophrenia, Autism, and 22q11.2 CNV Mediated Risk for Neuropsychiatric Disorders

2019 ◽  
Author(s):  
Jennifer K. Forsyth ◽  
Daniel Nachun ◽  
Michael J. Gandal ◽  
Daniel H. Geschwind ◽  
Ariana E. Anderson ◽  
...  
Keyword(s):  
Gene Networks ◽  
Disease Risk ◽  
Neuropsychiatric Disorders ◽  
Autism Spectrum ◽  
Synaptic Function ◽  
Protein Interaction Data ◽  
Regulatory Pathways ◽  
Polygenic Risk ◽  
Risk Variants ◽  
Gene Regulatory

AbstractBackground22q11.2 copy number variants (CNVs) are among the most highly penetrant genetic risk variants for developmental neuropsychiatric disorders such as schizophrenia (SCZ) and autism spectrum disorder (ASD). However, the specific mechanisms through which they confer risk remain unclear.MethodsUsing a functional genomics approach, we integrated transcriptomic data from the developing human brain, genome-wide association findings for SCZ and ASD, protein interaction data, and pathophysiological signatures of SCZ and ASD to: 1) organize genes into the developmental cellular and molecular systems within which they operate; 2) identify neurodevelopmental processes associated with polygenic risk for SCZ and ASD across the allelic frequency spectrum; and 3) elucidate pathways and individual genes through which 22q11.2 CNVs may confer risk for each disorder.ResultsPolygenic risk for SCZ and ASD converged on partially overlapping gene networks involved in synaptic function and transcriptional regulation, with ASD risk variants additionally enriched for networks involved in neuronal differentiation during fetal development. The 22q11.2 locus formed a large protein network that disproportionately affected SCZ- and ASD-associated neurodevelopmental networks, including loading highly onto synaptic and gene regulatory pathways. SEPT5, PI4KA, and SNAP29 genes are candidate drivers of 22q11.2 synaptic pathology relevant to SCZ and ASD, and DGCR8 and HIRA are candidate drivers of disease-relevant alterations in gene regulation.ConclusionsThe current approach provides a powerful framework to identify neurodevelopmental processes affected by diverse risk variants for SCZ and ASD, and elucidate the mechanisms through which highly penetrant multi-gene CNVs contribute to disease risk.

Prenet: Predictive network from ATAC-SEQ data

2020 ◽  
Vol 18 (01) ◽  
pp. 2040003 ◽  
Author(s):  
Nazmus Salehin ◽  
Patrick P. L. Tam ◽  
Pierre Osteil
Keyword(s):  
Regulatory Network ◽  
State Of The Art ◽  
Cell Types ◽  
Cell Type ◽  
Regulatory Pathways ◽  
Novel Approach ◽  
Multiple Cell ◽  
Bona Fide ◽  
Gene Regulatory ◽  
Accessible Chromatin

Assays for transposase-accessible chromatin sequencing (ATAC-seq) provides an innovative approach to study chromatin status in multiple cell types. Moreover, it is also possible to efficiently extract differentially accessible chromatin (DACs) regions by using state-of-the-art algorithms (e.g. DESeq2) to predict gene activity in specific samples. Furthermore, it has recently been shown that small dips in sequencing peaks can be attributed to the binding of transcription factors. These dips, also known as footprints, can be used to identify trans-regulating interactions leading to gene expression. Current protocols used to identify footprints (e.g. pyDNAse and HINT-ATAC) have shown limitations resulting in the discovery of many false positive footprints. We generated a novel approach to identify genuine footprints within any given ATAC-seq dataset. Herein, we developed a new pipeline embedding DACs together with bona fide footprints resulting in the generation of a Predictive gene regulatory Network (PreNet) simply from ATAC-seq data. We further demonstrated that PreNet can be used to unveil meaningful molecular regulatory pathways in a given cell type.

scholarly journals A common cell-type specific surface antigen in cultured human glial cells and fibroblasts: loss in malignant cells.

1976 ◽  
Vol 143 (1) ◽  
pp. 64-72 ◽  
Author(s):  
A Vaheri ◽  
E Ruoslahti ◽  
B Westermark ◽  
J Ponten
Keyword(s):  
Cell Surface ◽  
Glial Cells ◽  
Surface Antigen ◽  
Malignant Gliomas ◽  
Human Tumor ◽  
Cellular Protein ◽  
Oncogenic Viruses ◽  
Extracellular Medium ◽  
Cultured Fibroblasts ◽  
Tumor Material

Fibroblast surface antigen (SFA) is a high molecular weight protein antigen, first shown on the surface of cultured fibroblasts in fibrillar structures. It is shed to the extracellular medium and also present in the circulation (serum and plasma). Fibroblasts transformed by tumor viruses produce SFA but do not retain it on cell surface. In this report we show that SFA is also present in cultured nonestablished astroglial cells. The glial and fibroblast SFAs are immunologically indistinguishable. Glial cells (three different nonestablished lines) contain more SFA per milligram cellular protein than fibroblasts. SFA was located on cell surface in fibrillar striae that frequently extended out from the cell body. Fluorescence was also found intracellularly in the cytoplasm. Malignant gliomas (astrocytomas) established to grow in culture from human tumor material produced SFA into the growth medium but had very little (lines U-105 MG and U-343 MG) or no detectable (lines U-118 MG, U-251 MG, and U-343 MG-a) cell surface SFA. In cultures of the glioma cells many cells, in particular those that appeared to be in the telophase stage, stained strongly positive for intracellular cytoplasmic SFA. These data demonstrate that similar to fibroblasts transformed experimentally by oncogenic viruses, cells grown from naturally occurring human tumors (glioblastomas) produce SFA but lose ability to retain it on cell surface.

Expression profile and potential regulatory pathways of SFTPA1 in human tumors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15675-e15675
Author(s):  
Lu Yuan ◽  
Mi Yang ◽  
Xixi Wu ◽  
Wenqi Huang ◽  
Yuting Wu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Expression Profile ◽  
Critical Role ◽  
Human Tumor ◽  
Lung Squamous Cell Carcinoma ◽  
Surfactant Protein ◽  
Functional Heterogeneity ◽  
Regulatory Pathways ◽  
Tumor Tissues ◽  
Potential Biomarker

e15675 Background: Pulmonary surfactant protein A1(SFTPA1) plays a critical role in maintaining lung tissue homeostasis and its disruption could cause lung diseases and even lung cancer. Despite the finding that SFTPA1 is a potential biomarker for lung cancer, the expression profile and molecular mechanism of SFTPA1 in pan-cancer remain unclear. Methods: The expression of SFTPA1 in BALB/c mice, human normal tissues and human tumor tissues were explored by immunohistochemistry assay. The prognostic values were evaluated by Kaplan-Meier Plotter Database Analysis. Principal components analysis and GO and KEGG pathway enrichment analyses were exerted to identify the functional heterogeneity of SFTPA1 in various tumors. Multiple databases were used to analyze immune infiltrates and regulation networks of SFTPA1. Results: This study described the expression profile of SFTPA1 in various organs and tissues of BALB/c mice and various types of human tumor tissues. Interestingly, we found the expression level of SFTPA1 mRNA was associated with different prognosis in different cancers, even in Lung adenocarcinoma(LUAD) and Lung squamous cell carcinoma(LUSC). The further analysis confirmed a functional heterogeneity of SFTPA1 across diverse cancer types. Significantly, SFTPA1 might regulate tumor microenvironment by affecting the polarization of M2 macrophages in LUAD and LUSC. Furthermore, we found the has-miR-3200-3p-HNF1B-SFTPA1 network was a potential upstream regulatory mechanism of SFTPA1 in LUSC. Conclusions: Our study elaborated expression profile and potential regulatory pathways of SFTPA1 in human solid cancers, and might provide a potential immune infiltration biomarker for lung cancer.

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