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Influence of LIN28 on let-7 expression in the papillary thyroid cancer.

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Aline Nogueira Olivé
Total Authors: 1
Document type: Master's Dissertation
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
Defense date:
Examining board members:
Dania Emi Hamassaki; Patricia Pereira Coltri; Ileana Gabriela Sanchez de Rubio
Advisor: Edna Teruko Kimura

In papillary thyroid cancer (PTC) changes in MAPK (Mitogen-Activated Protein Kinase) pathway are common being BRAFT1799A mutation the most frequent alteration. MAPK pathway is modulated by miRNA such as let-7, an under-expressed miRNA in PTC. The RNA binding protein LIN28 controls let-7 biogenesis, blocking primary and precursor let-7 (pri-let-7 e pre-let-7) processing. We evaluated LIN28, pri-let-7f, pre-let-7f and let-7f gene expression by real time RTPCR using total RNA of human PTC sample and PTC cell lines TPC-1 and BCPAP. Non-tumoral cell line Nthyori 3-1 was used to evaluate LIN28B influence in let-7f. We observed decreased let-7f expression in 4 out of 5 PTC patients, and increased LIN28A in 2 patients with BRAFT1799A mutation. TPC-1 cells express higher levels of pri-let-7f while pre-let-7f and let-7f are less expressed. We noted that LIN28A is more expressed in TPC-1, while LIN28B is more expressed in BCPAP cells with BRAFT1799A. The inhibition of BRAFV600E in BCPAP decreases LIN28B and increases let-7f, while the induction of LIN28B in Nthyori 3-1 reduces let-7f expression. We conclude there is an inverse association between LIN28 and let-7f in PTC, and that LIN28 influences let-7f reduction which could contribute to thyroid tumorigenesis. (AU)

FAPESP's process: 12/14325-6 - Influence of LIN28 " RNA-binding protein" in the thyroid oncogenesis
Grantee:Aline Nogueira Olivé
Support Opportunities: Scholarships in Brazil - Master