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Título

CRUCIAL ROLE OF MICRORNAS -221 AND -222 AND THEIR TARGET GENE P27KIP1 IN PROSTATE CANCER PROGRESSION

Introdução, Material, Método, Resultados, Discussão e Conclusões

Introduction: The cyclin-dependent kinase inhibitor p27Kip1 has been suggested as a prognostic marker in prostate cancer (PCa). In this study, our aim was to demonstrate the signature of the microRNAs -221 and -222 and the p27Kip1 gene in addition to the AR gene. Using surgical specimens of primary cancer patients who responded to hormone therapy and patients who evolved to resistance to castration and correlate this expression with the classic prognostic factors of PCa. Method: MicroRNAs and genes expression levels of the surgical specimens were analyzed by q-PCR. This study was performed using 44 samples of surgical specimens from patients with clinically localized PCa who underwent radical prostatectomy, with a mean follow-up time of 94.32 months. Of the 44 patients, only nine responded to hormone therapy for at least 1 year, and 35 patients were resistant to hormone therapy in less than 1 year of treatment and showed disease recurrence. Control group consisted of five patients who had no diagnosis of PCa (negative biopsy) Results: MicroRNAs -221 and -222 were underexpressed in surgical specimens of PCa, in 93,18% e 54,55% respectively; however, their target gene, p27Kip1, was overexpressed in 100% of the cases, as so how o AR gene. Higher microRNAs expression was associated with prognostic factors: PSA ≥10ng/mL and higher tumor percentage of the specimen (p≤0.05). miR-221 showed higher expression associated with tumor volumes ≥15mm3 and miR-222 showed higher expression in the ISUP 1-2 group (p≤0.05). p27Kip1 gene showed higher expression in the group of patients characterized as sensitive (p=0.05), as well as the AR gene (p<0.05). We averaged the expression of the p27Kip1 and AR genes and observed the relationship of recurrence-free survival time to the expression of these genes. We present that those patients who had higher expression of both p27Kip1 gene and RA had longer recurrence-free survival time (p <0.05) (Figure 3). Conclusion: MicroRNAs -221 and -222 were underexpressed in surgical specimens of PCa, however, their target gene, p27Kip1, was overexpressed in 100% of the cases, as so how o AR gene. In our work, we confirmed the important role of microRNAs -221 / -222 in prostate carcinogenesis and highlighted the potential role of the p27Kip1 gene in tumor suppression. We believe that more studies that are detailed can contribute to the consolidation of the p27Kip1 gene as a good marker of tumor progression.

Palavras Chave

Prostate Cancer, microRNA, miR-221, miR-222, p27Kip1, AR, CDKN1B, biomarker

Área

Câncer de Próstata Localizado

Instituições

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

Autores

Ruan Pimenta, Nayara I Viana, Vanessa R Guimaraes, Gustavo Inoue, Gabriel A G D dos Santos, Vinicius G dos Santos, Iran A Silva, Katia R M Leite, Miguel Srougi, Sabrina T Reis