Efeitos celular e molecular de peptídeo mimético à Argonauta 4 em linhagens celulares celulares protáticas

Abstract

Prostate cancer (PCa) is an important public health problem with increasing incidence and mortality rates. The early diagnosis is essential for curing. However, the disease is challenge due to no specific symptoms and slow progression. In this scenario, non-coding RNAs have emerged as key molecules for understanding the tumor biology. Notably the Prostate Cancer Associated 3 (PCA3), a long non-coding RNA (lncRNA), is a specific marker for PCa, associated with neoplastic cell control, hormone regulation, epithelial mesenchymal transition and angiogenesis processes. In this context, is needed to better understand its transcriptional mechanism to define new therapeutic targets. We explored Phage Display nanoplatform for the discovery of PCA3 regulatory ligands, aiming to modulate its expression. Mimetic peptides to Argonauta 4 (AGO4) were previously selected by our group. In the present study, we evaluated the effects of AGO4 mimetic phages in prostate cells through MTT assays. For RWPE-1 (nontumorigenic) cell line, treatments for 24 hours at 10⁵ cfu and 48 hours at 10⁷ cfu were cytotoxic (p< 0.05 and p< 0.01, respectively). For LNCaP (responsive hormone) cell line, treatment for 24 hours with 10⁵ cfu decreased cell viability, and with 10⁹ cfu (p< 0.01) presented proliferative effect. For PC3 (castration resistant) cell line, after 48 hours, phages titrated at 10⁵ cfu induced cell proliferation (p< 0.05). Considering qPCR assays, AGO4, PRUNE2 and PCA3 genes are overexpressed in LNCaP lineage compared to PC3. After treatment with phage particles, no change in AGO4 mimetic peptide-mediated expression was observed. As PCA3 expression is regulated by androgens, we suggest that further studies may be performed without serum supplementation. In addition, other transcriptional factors should also be included as we hypothesize that AGO4 alone do not activate PCA3 expression.