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Evaluation of the expression profile of microRNAs in reticulocytes and in CD34(+)-derived erythroid cells from individuals with HPFH-2 and patients with Sicilian Delta-beta-thalassemia

Grant number: 13/06679-5
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): July 01, 2013
Effective date (End): June 30, 2016
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Fernando Ferreira Costa
Grantee:Thais Arouca Fornari Tavares
Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil


Changes in hemoglobin known as Hemoglobinopathies, are a heterogeneous group of genetic disorders caused by mutations that affect the genes responsible for the chains encoding. The Hereditary Persistence of Fetal Hemoglobin (HPFH) is one of these groups without significant clinical manifestations resulting in high levels of HbF in adult life. Such molecular changes occur in the group of beta globin genes and can be divided into two categories: deletional and non-deletional HPFH forms. Two deletions related to HPFH (HPFH-1 and HPFH-2) have been described in the Brazilian population according to studies conducted in screening tests of the Blood Center and the Clinics Hospital of Unicamp. The Delta-beta-thalassaemias are also originated from deletions in many cases quite similar to the ones that originate the deletional HPFH forms. Some hypotheses can be proposed to explain the relation of HPFH deletions related to the lack of normal suppression of gama genes in adulthood and one of them is related to post-transcriptional control and the action of microRNAs. Such molecules may be responsible for this regulation mechanism affecting the differential expression of the globins and some of transcription factors that regulate them. In this project, we will investigate this possible gene regulation mechanism in both reticulocyte and in CD34(+)-derived erythroid cells, evaluating the differential expression profile of microRNAs. Subsequently, we will evaluate the effect of the blocking and / or induction of some of these small RNAs on the expression of the globins (alfa, beta and gama) and of some transcription factors such as ARID1B, and TSPYL1 ZHX2 that are potential candidates as globins regulators. This research can help understanding the phenotypic differences found between delecional HPFH and Delat-beta-thalassemia.

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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)
FORNARI, THAIS A.; LANARO, CAROLINA; ALBUQUERQUE, DULCINEIA M.; FERREIRA, REGIANE; COSTA, FERNANDO F.. Modulation of fetal hemoglobin in hereditary persistence of fetal hemoglobin deletion type-2, compared to Sicilian delta beta-thalassemia, by BCL11A and SOX6-targeting microRNAs. Experimental Biology and Medicine, v. 242, n. 3, p. 267-274, . (13/06679-5)

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