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Reconstruction of gene regulation networks involved in cancer cachexia: integrating expression profiles of microRNAs and mRNA

Grant number: 13/02005-0
Support Opportunities:Scholarships abroad - Research Internship - Master's degree
Effective date (Start): April 05, 2013
Effective date (End): July 04, 2013
Field of knowledge:Biological Sciences - Morphology - Histology
Principal Investigator:Robson Francisco Carvalho
Grantee:Geysson Javier Fernandez Garcia
Supervisor: Kathleen Marchal
Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Research place: Ghent University (UGent), Belgium  
Associated to the scholarship:11/16282-0 - Genomic Profiling of Messenger RNAs and MicroRNAs in muscle cells treated in vitro with TNF-alpha and IFN-gamma, BP.MS


The skeletal muscle atrophy is a common phenomenon in many chronic systemic diseases such as sepsis, chronic heart failure, chronic obstructive pulmonary disease, chronic kidney disease, diabetes, AIDS and cancer. These diseases can be accompanied by a complex metabolic syndrome characterized by muscle wasting, known as cachexia. The molecular pathways responsible for cachexia are not completely understood, however, evidence suggests that proinflammatory cytokines such as tumor necrosis factor (TNF) - alpha and interferon (INF) -gamma have a key role in molecular pathways related to loss of function and muscle mass. The complexity of the mechanisms controlling gene expression in this process suggests the involvement of additional regulatory molecules, such as micro-RNAs; these RNA molecules encoded by the genome regulate various cellular processes of skeletal muscle and are involved in various muscular diseases. miRNAs work in concert to control a common pathway or biological function, this unique feature of miRNAs make them effective tools for determining the pathways involved in specific diseases or biological processes. Our hypothesis is that skeletal muscle atrophy induced by TNF-alpha and IFN-gamma has a characteristic profile of expression of miRNAs and mRNAs, which enable the identification of regulatory networks and molecular pathways involved in muscle wasting. The microRNAs and mRNA expression data have been obtained by our laboratory using the TaqMan Rodent miRNA Array cards and next generation sequencing, respectively. In this context, the internship in the laboratory of Professor Dr. Kathleen Marchal aims to analyze the expression profile of miRNAs and mRNA in cachexia induced by cytokines and will make an analysis of regulatory networks inferred from gene expression data of miRNA and mRNA, using the recently inference modules networks algorithm based on probabilistic optimization techniques developed by the group of Dr. Marchal. The results anticipated by this internship will be critical to guide the next steps in the validation of the biological role of these miRNAs in cachexia, and in the short term we going to analyze the networks that were actually predicted regulated: using qPCR, Western blot analysis and functional analysis. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FERNANDEZ, GEYSSON JAVIER; FERREIRA, JUAREZ HENRIQUE; VECHETTI JR, IVAN JOSE; DE MORAES, LEONARDO NAZARIO; CURY, SARAH SANTILONI; FREIRE, PAULA PACCIELLI; GUTIERREZ, JAYSON; FERRETTI, RENATO; DAL-PAI-SILVA, MAELI; ROGATTO, SILVIA REGINA; et al. MicroRNA-mRNA Co-sequencing Identifies Transcriptional and Post-transcriptional Regulatory Networks Underlying Muscle Wasting in Cancer Cachexia. FRONTIERS IN GENETICS, v. 11, . (13/02005-0, 12/13961-6, 13/50343-1, 16/08294-1, 14/13941-0, 11/16282-0)

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