Identification of Long Noncoding RNAs Deregulated in Papillary Thyroid Cancer and Correlated with BRAF(V600E) Mutation by Bioinformatics Integrative Analysis

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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 ; de Castro, Marcela Motta ; Kimura, Edna Teruko ; Silva, Jr., Wilson Araujo ; Espreafico, Enilza Maria

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 7, MAY 10 2017.
• Web of Science Citations: 12

Abstract

Papillary Thyroid Cancer (PTC) is an endocrine malignancy in which BRAF(V600E) oncogenic mutation induces the most aggressive phenotype. In this way, considering that lncRNAs are arising as key players in oncogenesis, it is of high interest the identification of BRAF(V600E)-associated long noncoding RNAs, which can provide possible candidates for secondary mechanisms of BRAF-induced malignancy in PTC. In this study, we identified differentially expressed lncRNAs correlated with BRAF(V600E) in PTC and, also, extended the cohort of paired normal and PTC samples to more accurately identify differentially expressed lncRNAs between these conditions. Indirectly validated targets of the differentially expressed lncRNAs in PTC compared to matched normal samples demonstrated an involvement in surface receptors responsible for signal transduction and cell adhesion, as well as, regulation of cell death, proliferation and apoptosis. Targets of BRAF(V600E)-correlated lncRNAs are mainly involved in calcium signaling pathway, ECM-receptor interaction and MAPK pathway. In summary, our study provides candidate lncRNAs that can be either used for future studies related to diagnosis/prognosis or as targets for PTC management. (AU)

• FAPESP's process: 14/07726-0 - Genomic and functional characterization of genes with expression restricted to melanoma (RMELs)
• Grantee: Lucas Goedert
• Support type: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 15/13396-5 - Drosophila melanogaster as a model for the study of cancer and degenerative diseases: The functional study of DmelEMC1 gene and the genetic interactions with other EMC complex members
• Grantee: Maiaro Cabral Rosa Machado
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 13/08135-2 - CTC - Center for Cell-Based Therapy
• Grantee: Dimas Tadeu Covas
• Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 14/50521-0 - Transcriptional regulation of miR-17-92 microRNA in aggressive thyroid cancer
• Grantee: Cesar Seigi Fuziwara
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 14/18189-5 - Studying a possible functional circuitry involving microRNAs, MITF, MYO5A/DLC2, RAB27A and connections with the invasion and metastasis cascade
• Grantee: Enilza Maria Espreafico
• Support type: Regular Research Grants