Publications

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3 Publications visible to you, out of a total of 3

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

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

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

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