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Transcriptional regulation of miR-17-92 microRNA in aggressive thyroid cancer

Grant number: 14/50521-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): September 01, 2014
Effective date (End): August 31, 2018
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal researcher:Edna Teruko Kimura
Grantee:Cesar Seigi Fuziwara
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):17/01829-0 - Study the role of microRNA in cancer metastasis using genetically engineered mouse models, BE.EP.PD


Genetic alterations in oncogenes and tumor supressor genes deregulate signaling pathways involved in proliferation, apoptosis and cell survival. Recently, microRNAs (miRNAs), small endogenous RNA that negatively regulate specific target mRNAs translation, have been implicated in oncogenesis, The expression of some miRNAs is associated to more aggressive cancers such as the cluster of miRNAs miR-17-92, detected in high levels in anaplastic thyroid cancer, the most aggressive of thyroid gland. Moreover, a certain fraction of papillary thyroid cancer shows miR-17-92 deregulation and aggressive behavior such as refractoriness to radioiodine therapy as anaplastic cells, being BRAF mutation a common feature in these cases. BRAFT1799A is the most frequent genetic alteration in thyroid cancer (2, 3) and induces miR-17-92 expression (4). Besides that, the knowledge of molecular activation/inhibition of miRNA transcription is not satisfactory. In silico studies show the presence of CpG islands in more than 50% of miRNA genes, indicating a potential epigenetic regulation. Therefore, in this project, we will study the molecular mechanisms involved in the transcription of miR-17-92 in thyroid cancer, investigating the role of epigenetic modifications such as methylation of CpG islands, modifications in histones of promoter region triggered by IncRNAs (long non-coding RNAs) and the role of transcription factors. Thus, we expect to contribute to the better understanding of molecular mechanism underlying transcription of miR-17-92 and its role in cancer progression, that would support the translational application of miRNA modulation in the treatment of patients with aggressive and refractory cancer. (AU)

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Scientific publications (5)
(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)
FUZIWARA, CESAR SEIGI; SAITO, KELLY CRISTINA; LEONI, SUZANA GARCIA; LOGULLO WAITZBERG, ANGELA FLAVIA; KIMURA, EDNA TERUKO. The Highly Expressed FAM83F Protein in Papillary Thyroid Cancer Exerts a Pro-Oncogenic Role in Thyroid Follicular Cells. FRONTIERS IN ENDOCRINOLOGY, v. 10, . (16/17129-4, 13/11019-4, 14/50521-0)
GOEDERT, LUCAS; PLACA, JESSICA RODRIGUES; FUZIWARA, CESAR SEIGI; ROSA MACHADO, MAIARO CABRAL; PLACA, DESIREE RODRIGUES; ALMEIDA, PALLOMA PORTO; SANCHES, TALITA PEREZ; DOS SANTOS, JAIR FIGUEREDO; CORVELONI, AMANDA CRISTINA; GOMES PEREIRA, ILLY ENNE; et al. Identification of Long Noncoding RNAs Deregulated in Papillary Thyroid Cancer and Correlated with BRAF(V600E) Mutation by Bioinformatics Integrative Analysis. SCIENTIFIC REPORTS, v. 7, . (15/13396-5, 13/08135-2, 14/18189-5, 14/50521-0, 14/07726-0)
FUZIWARA, CESAR SEIGI; KIMURA, EDNA TERUKO. MicroRNAs in thyroid development, function and tumorigenesis. Molecular and Cellular Endocrinology, v. 456, n. C, SI, p. 44-50, . (16/17129-4, 13/11019-4, 14/50521-0)
FUZIWARA, CESAR SEIGI; KIMURA, EDNA TERUKO. Insights into regulation of the miR-17-92 cluster of miRNAs in cancer. FRONTIERS IN MEDICINE, v. 2, . (13/11019-4, 14/50521-0)
CESAR SEIGI FUZIWARA; KELLY CRISTINA SAITO; EDNA TERUKO KIMURA. Interplay of TGFβ signaling and microRNA in thyroid cell loss of differentiation and cancer progression. ARCHIVES OF ENDOCRINOLOGY METABOLISM, v. 63, n. 5, p. 536-544, . (16/17129-4, 14/50521-0)

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