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Título

ANTI-MIR-221 AND ANTI-MIR-222 INHIBITS CELL PROLIFERATION IN PC3, PROSTATE CANCER CELL LINE BY INDUCING P27KIP1 EXPRESSION

Introdução, Material, Método, Resultados, Discussão e Conclusões

Introduction: p27Kip1 (CDKN1B) has been emerged as an important transcriptional regulator, associated with essential cellular functions as cell division cycle, respiration, RNA processing, translation and cell adhesion. Its deregulation has been involved in cancer and neurodegeneration. OncomiRs 221 and 222 have as target p27kip1 and are, also involved in tumorigenesis in many organs. Our aim was to evaluate the role of anti-miRNAs 221 and 222 and their target gene p27kip1 in castration-resistant (PC-3) PCa cell line. Method: PC3, castration-resistant cell line was transfected with anti-miR-221, 222 and their scrambled controls using Lipofectamine RNA iMAX (Invitrogen®). The cell cycle assays were performed by flow cytometry. Results: Following transfection of anti-miR-221 and 222, there was a significant increase in p27kip1 gene expression, p=0,003 and p=0,0004, respectively. The cell cycle assays showed an increase of cells in G0/G1 phase, p=0.009 for anti-miR-221 and p=0.0007 for anti-miR-222 and a significant reduction in G2/M phase (p=0.0004) for both anti-miRs. Proliferation was also decreased after transfection of both anti-miRs (p=0.0003). Conclusion: p27Kip1 control by miR-221 and 222 may play an important role in the progression of PCa, since the inhibition of these microRNAs resulted in the interruption of the cell cycle (increased cell rates in G0 / G1 and reduction in G2 / M) and lower rates of proliferation.

Palavras Chave

Prostate Cancer; microRNA; miR-221; miR-222, p27kip1; cell cycle

Área

Câncer de Próstata Metastático

Instituições

Faculdade de Medicina da Universidade de São Paulo - Sao Paulo - Brasil

Autores

Nayara I Viana, Ruan Pimenta, Vanessa R Guimarães, Juliana A Camargo, Gabriela Q Amaral, Vitoria G Nunes, Iran A Silva, Katia R M Leite, Miguel Srougi, Sabrina T Reis