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5 Publications visible to you, out of a total of 5
Developing A Virus-MicroRNA Interactome Using Cystoscope

Abstract (Expand)

It is currently difficult to determine the effect of oncogenic viruses on the global function and regulation of pathways within mammalian cells. A thorough understanding of the molecular pathways and … individual genes altered by oncogenic viruses is needed for the identification of targets that can be utilised for early diagnosis, prevention, and treatment methods. We detail a logical step-by-step guide to uncover viral-protein-miRNA interactions using publically available datasets and the network building program, Cytoscape. This method may be applied to identify specific pathways that are altered in viral infection, and contribute to the oncogenic transformation of cells. To demonstrate this, we constructed a gene regulatory interactome encompassing Human Papillomavirus Type 16 (HPV16) and its control of specific miRNAs. This approach can be broadly applied to understand and map the regulatory functions of other oncogenic viruses, and determine their role in altering the cellular environment in cancer.

Authors: Meredith Hill, Dayna Mason, Tânia Monteiro Marques, Margarida Gama Carvalho, Nham Tran

Date Published: 1st Oct 2019

Publication Type: Not specified

Searching the overlap between network modules with specific betweeness (S2B) and its application to cross-disease analysis

Abstract (Expand)

Discovering disease-associated genes (DG) is strategic for understanding pathological mechanisms. DGs form modules in protein interaction networks and diseases with common phenotypes share more DGs or … have more closely interacting DGs. This prompted the development of Specific Betweenness (S2B) to find genes associated with two related diseases. S2B prioritizes genes frequently and specifically present in shortest paths linking two disease modules. Top S2B scores identified genes in the overlap of artificial network modules more than 80% of the times, even with incomplete or noisy knowledge. Applied to Amyotrophic Lateral Sclerosis and Spinal Muscular Atrophy, S2B candidates were enriched in biological processes previously associated with motor neuron degeneration. Some S2B candidates closely interacted in network cliques, suggesting common molecular mechanisms for the two diseases. S2B is a valuable tool for DG prediction, bringing new insights into pathological mechanisms. More generally, S2B can be applied to infer the overlap between other types of network modules, such as functional modules or context-specific subnetworks. An R package implementing S2B is publicly available at https://github.com/frpinto/S2B.

Authors: Marina L. Garcia-Vaquero, Margarida Gama-Carvalho, Javier De Las Rivas, Francisco R. Pinto

Date Published: 1st Dec 2018

Publication Type: Not specified

Human papillomavirus 16 E6 modulates the expression of miR-496 in oropharyngeal cancer.

Abstract (Expand)

Human papillomavirus (HPV), notably type 16, is a risk factor for up to 75% of oropharyngeal squamous cell carcinomas (SCC). It has been demonstrated that small non-coding RNAs known as microRNAs play … a vital role in the cellular transformation process. In this study, we used an LNA array to further investigate the impact of HPV16 on the expression of microRNAs in oropharyngeal (tonsillar) cancer. A number of miRNAs were found to be deregulated, with miR-496 showing a four-fold decrease. Over-expression of the high risk E6 oncoprotein down-regulated miR-496, impacting upon the post-transcriptional control of the transcription factor E2F2. These HPV specific miRNAs were integrated with the HPV16 interactome to identify possible mechanistic pathways. These analyses provide insights into novel molecular interactions between HPV16 and miRNAs in oropharyngeal cancers.

Authors: D. Mason, X. Zhang, T. M. Marques, B. Rose, S. Khoury, M. Hill, F. Deutsch, J. G. Lyons, M. Gama-Carvalho, N. Tran

Date Published: 24th Jun 2018

Publication Type: Not specified

miRNA profiling of human naive CD4 T cells links miR-34c-5p to cell activation and HIV replication.

Abstract (Expand)

Cell activation is a vital step for T-cell memory/effector differentiation as well as for productive HIV infection. To identify novel regulators of this process, we used next-generation sequencing to … profile changes in microRNA expression occurring in purified human naive CD4 T cells in response to TCR stimulation and/or HIV infection. Our results demonstrate, for the first time, the transcriptional up-regulation of miR-34c-5p in response to TCR stimulation in naive CD4 T cells. The induction of this miR was further consistently found to be reduced by both HIV-1 and HIV-2 infections. Overexpression of miR-34c-5p led to changes in the expression of several genes involved in TCR signaling and cell activation, confirming its role as a novel regulator of naive CD4 T-cell activation. We additionally show that miR-34c-5p promotes HIV-1 replication, suggesting that its down-regulation during HIV infection may be part of an anti-viral host response.

Authors: A. J. Amaral, J. Andrade, R. B. Foxall, P. Matoso, A. M. Matos, R. S. Soares, C. Rocha, C. G. Ramos, R. Tendeiro, A. Serra-Caetano, J. A. Guerra-Assuncao, M. Santa-Marta, J. Goncalves, M. Gama-Carvalho, A. E. Sousa

Date Published: 1st Feb 2017

Publication Type: Not specified

Linking amyotrophic lateral sclerosis and spinal muscular atrophy through RNA-transcriptome homeostasis: a genomics perspective.

Abstract (Expand)

In this review, we present our most recent understanding of key biomolecular processes that underlie two motor neuron degenerative disorders, amyotrophic lateral sclerosis, and spinal muscular atrophy. … We focus on the role of four multifunctional proteins involved in RNA metabolism (TDP-43, FUS, SMN, and Senataxin) that play a causal role in these diseases. Recent results have led to a novel scenario of intricate connections between these four proteins, bringing transcriptome homeostasis into the spotlight as a common theme in motor neuron degeneration. We review reported functional and physical interactions between these four proteins, highlighting their common association with nuclear bodies and small nuclear ribonucleoprotein particle biogenesis and function. We discuss how these interactions are turning out to be particularly relevant for the control of transcription and chromatin homeostasis, including the recent identification of an association between SMN and Senataxin required to ensure the resolution of DNA-RNA hybrid formation and proper termination by RNA polymerase II. These connections strongly support the existence of common pathways underlying the spinal muscular atrophy and amyotrophic lateral sclerosis phenotype. We also discuss the potential of genome-wide expression profiling, in particular RNA sequencing derived data, to contribute to unravelling the underlying mechanisms. We provide a review of publicly available datasets that have addressed both diseases using these approaches, and highlight the value of investing in cross-disease studies to promote our understanding of the pathways leading to neurodegeneration.

Authors: M. Gama-Carvalho, M. L Garcia-Vaquero, F. R Pinto, F. Besse, J. Weis, A. Voigt, J. B. Schulz, J. De Las Rivas

Date Published: 6th Jan 2017

Publication Type: Not specified

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