Prostate cancer (PCa) is the second-leading cause of cancer-related death among men. microRNAs have been identified as having potential roles in tumorigenesis. An oncomir, miR-21, is commonly highly upregulated in many cancers, including PCa, and showed correlation with the Wnt-signaling axis to increase invasion. Wnt-11 is a developmentally regulated gene and has been found to be upregulated in PCa, but its mechanism is unknown. The present study aimed to investigate the roles of miR-21 and Wnt-11 in PCa in vivo and in vitro. First, different Gleason score PCa tissue samples were used; both miR-21 and Wnt-11 expressions correlate with high Gleason scores in PCa patient tissues. This data then was confirmed with formalin-fixed paraffin cell blocks using PCa cell lines LNCaP and PC3. Cell survival and colony formation studies proved that miR-21 involves in cells’ behaviors, as well as the epithelial-mesenchymal transition. Consistent with the previous data, silencing miR-21 led to significant inhibition of cellular invasiveness. Overall, these results suggest that miR-21 plays a significant role related to Wnt-11 in the pathophysiology of PCa.

Photobacterium damselae subsp. piscicida (Phdp) is a Gram-negative bacterium that infects a large number of marine fish species in Europe, Asia, and America, both in aquacultures and in the natural environment. Among the affected hosts are economically important cultured fish, such as sea bream (Sparus aurata), sea bass (Dicentrarchus labrax), yellowtail (Seriola quinqueradiata), and cobia (Rachycentron canadum). The best characterized virulence factor of Phdp is the Apoptosis-Inducing Protein of 56 kDa (AIP56), a secreted AB-type toxin that has been shown to induce apoptosis of sea bass phagocytes during infection. AIP56 has an A subunit that displays metalloprotease activity against NF-kB p65 and a B subunit that mediates binding and internalization of the A subunit in susceptible cells. Despite the fact that the aip56 gene is highly prevalent in Phdp isolates from different fish species, the toxicity of AIP56 has only been studied in sea bass. In the present study, the toxicity of AIP56 for sea bream was evaluated. Ex vivo assays showed that sea bream phagocytes are resistant to AIP56 cytotoxicity and that resistance was associated with an inefficient internalization of the toxin by those cells. Accordingly, in vivo intoxication assays revealed that sea bream is much more resistant to AIP56-induced lethality than sea bass. These findings, showing that the effect of AIP56 is different in sea bass and sea bream, set the basis for future studies to characterize the effects of AIP56 and to fully elucidate its virulence role in different Phdp susceptible hosts.

The AB-type toxin AIP56 is a key virulence factor of Photobacterium damselae subsp. piscicida ( Phdp ), inducing apoptosis in fish immune cells. The discovery of AIP56-like and AIP56-related toxins in diverse organisms, including human-associated Vibrio strains, highlights the evolutionary conservation of this toxin family, suggesting that AIP56 and its homologs may share conserved receptors across species. These toxins have potential for biotechnological applications, such as therapeutic protein delivery and immune modulation. Herein, the cell specificity of AIP56 for immune cells in sea bass, mice, and humans was characterized. Whether AIP56 interacts directly or indirectly with sea bass neutrophils was never investigated and it was shown that only a small population of sea bass neutrophils internalized AIP56, indicating that most of the neutrophilic destruction during Phdp infection and/or AIP56 intoxication does not result from the direct toxicity of the toxin. Moreover, the cellular tropism of AIP56 for myeloid cells was observed in the three species, including its preference for macrophages. Further, mouse and human M0 and M2-like macrophages internalized more toxin than M1-like macrophages. Despite the limited interaction of lymphoid cells with AIP56, mouse B1-cells were able to internalize the toxin, possibly due to its myeloid features. These findings are relevant for both pathogenicity and biomedical contexts.