Prostate cancer is the most common cancer in men around the world. It is a complex and heterogeneous disease in which androgens and their receptors play a crucial role in the progression and development. The current treatment for prostate cancer is a combination of surgery, hormone therapy, radiation and chemotherapy. Therapeutic agents commonly used in the clinic include steroidal and non-steroidal anti-androgens, such as cyproterone acetate, bicalutamide and enzalutamide. These few agents have multiple adverse effects and are not 100% effective. Several plant compounds and mixtures, including grape seed polyphenol extracts, lycopene and tomato preparations, soy isoflavones, and green tea extracts, have been shown to be effective against prostate cancer cell growth. In vivo activity of some isolated compounds like capsaicin and curcumin was reported in prostate cancer murine models. We prepared a library of plant extracts from traditional Mayan medicine. These plants were selected for their use in the contemporaneous Mayan communities for the treatment of different diseases. The extracts were assessed in a phenotypic screening using LNCaP prostate cancer androgen sensitive cell line, with a fixed dose of 25 μg/mL. MTT assay identified seven out of ten plants with interesting anti-neoplastic activity. Extracts from these plants were subjected to a bioguided fractionation to study their major components. We identified three compounds with anti-neoplastic effects against LNCaP cells, one of which shows selectivity for neoplastic compared to benign cells.

Trypanosomatids are protozoan parasites that cause devastating vector-borne human diseases. Gene expression regulation of these organisms depends on post-transcriptional control in responding to diverse environments while going through multiple developmental stages of their complex life cycles. In this scenario, non-coding RNAs (ncRNAs) are excellent candidates for a very efficient, quick, and economic strategy to regulate gene expression. The advent of high throughput RNA sequencing technologies show the presence and deregulation of small RNA fragments derived from canonical ncRNAs. This review seeks to depict the ncRNA landscape in trypanosomatids, focusing on the small RNA fragments derived from functional RNA molecules observed in RNA sequencing studies. Small RNA fragments derived from canonical ncRNAs (tsRNAs, snsRNAs, sdRNAs, and sdrRNAs) were identified in trypanosomatids. Some of these RNAs display changes in their levels associated with different environments and developmental stages, demanding further studies to determine their functional characterization and potential roles. Nevertheless, a comprehensive and detailed ncRNA annotation for most trypanosomatid genomes is still needed, allowing better and more extensive comparative and functional studies.

Prostate cancer is a major health problem worldwide. MiR-183 is an oncomiR and a candidate biomarker in prostate cancer, affecting various pathways responsible for disease initiation and progression. We sought to discover the most relevant processes controlled by miR-183 through an unbiased transcriptomic approach using prostate cell lines and patient tissues to identify miR-183 responsive genes and pathways. Gain of function experiments, reporter gene assays, and transcript and protein measurements were conducted to validate predicted functional effects and protein mediators. A total of 135 candidate miR-183 target genes overrepresenting cell adhesion terms were inferred from the integrated transcriptomic analysis. Cell attachment, spreading assays and focal adhesion quantification of miR-183-overexpressing cells confirmed the predicted reduction in cell adhesion. ITGB1 was validated as a major target of repression by miR-183 as well as a mediator of cell adhesion in response to miR-183. The reporter gene assay and PAR-CLIP read mapping suggest that ITGB1 may be a direct target of miR-183. The negative correlation between miR-183 and ITGB1 expression in prostate cancer cohorts supports their interaction in the clinical set. Overall, cell adhesion was uncovered as a major pathway controlled by miR-183 in prostate cancer, and ITGB1 was identified as a relevant mediator of this effect.

MicroRNAs are small RNAs that regulate gene expression through complementary base pairing with their target mRNAs. A substantial understanding of microRNA target recognition and repression mechanisms has been reached using diverse empirical and bioinformatic approaches, primarily in vitro biochemical or cell culture perturbation settings. We sought to determine if rules of microRNA target efficacy could be inferred from extensive gene expression data of human tissues. A transcriptome-wide assessment of all the microRNA–mRNA canonical interactions’ efficacy was performed using a normalized Spearman correlation (Z-score) between the abundance of the transcripts in the PRAD-TCGA dataset tissues (RNA-seq mRNAs and small RNA-seq for microRNAs, 546 samples). Using the Z-score of correlation as a surrogate marker of microRNA target efficacy, we confirmed hallmarks of microRNAs, such as repression of their targets, the hierarchy of preference for gene regions (3′UTR > CDS > 5′UTR), and seed length (6 mer < 7 mer < 8 mer), as well as the contribution of the 3′-supplementary pairing at nucleotides 13–16 of the microRNA. Interactions mediated by 6 mer + supplementary showed similar inferred repression as 7 mer sites, suggesting that the 6 mer + supplementary sites may be relevant in vivo. However, aggregated 7 mer-A1 seeds appear more repressive than 7 mer-m8 seeds, while similar when pairing possibilities at the 3′-supplementary sites. We then examined the 3′-supplementary pairing using 39 microRNAs with Z-score-inferred repressive 3′-supplementary interactions. The approach was sensitive to the offset of the bridge between seed and 3′-supplementary pairing sites, and the pattern of offset-associated repression found supports previous findings. The 39 microRNAs with effective repressive 3′supplementary sites show low GC content at positions 13–16. Our study suggests that the transcriptome-wide analysis of microRNA–mRNA correlations may uncover hints of microRNA targeting determinants. Finally, we provide a bioinformatic tool to identify microRNA–mRNA candidate interactions based on the sequence complementarity of the seed and 3′-supplementary regions.

Plasmalogens are a unique class of glycerophospholipids defined by a distinctive vinyl ether bond. While these lipids are abundant in animals and important for human health, their evolutionary history remains enigmatic, mostly due to their absence in some major eukaryotic lineages like plants. Here, we resolve the origin and evolution of the aerobic plasmalogen biosynthesis pathway in eukaryotes. Through comprehensive phylogenomic analysis and experimental validation of enzyme activity and plasmalogen presence, we demonstrate that the essential desaturase plasmanylethanolamine desaturase 1 (PEDS1)—and likely the fatty acyl-CoA reductase (FAR) and glycerone phosphate O -acyltransferase (GNPAT) enzymes also critical in the pathway—were acquired by an early eukaryotic ancestor through horizontal gene transfer (HGT) from myxobacteria. Our data show that this bacterial pathway was retained in the Amorphea and Discoba supergroups but lost or replaced in others. The findings yield insights into how HGT shaped metabolic pathways in early eukaryotes.

How novel proteins and protein architectures evolve is a central question in evolutionary biology. Early-branching trypanosomatids provide a valuable system to investigate this process because they retain ancestral eukaryotic features while also encoding lineage-specific proteins with unknown evolutionary origins. Among these, the Dispersed Gene Family 1 (DGF-1) is one of the largest and most enigmatic multigene families, characterized by its exceptional size, repetitive organization, and poorly understood biological function. We performed a comprehensive structural and evolutionary analysis of DGF-1 and identified a previously unrecognized modular architecture composed of 7 tandemly repeated structural domains, here termed ribs, that form a huge extracellular protrusion, followed by a conserved C-terminal membrane-associated region containing a hat domain and multiple transmembrane helices. To investigate the origin of this architecture, each structural module, as well as the complete protein, was searched across the Discoba supergroup using both sequence- and structure-based remote homology searches. These analyses revealed that the DGF-1 architecture did not originate in free-living kinetoplastids. Instead, the free-living kinetoplastid Bodo saltans contains proteins harboring only rib-like domains and other proteins containing the membrane-associated region, whereas the first complete DGF-1 architecture appears in the early-branching trypanosomatid Paratrypanosoma confusum. Within trypanosomatids, the 7 rib modules are highly conserved across paralogous copies and cluster according to their position within the protein, indicating that the canonical 7-rib architecture predates the emergence of bona fide DGF-1 proteins. Comparative genomic analyses further show that DGF-1 genes were retained in some species, independently expanded in others with its largest expansion occurring in Trypanosoma cruzi, or secondarily lost in different lineages (leishmania and African trypanosomes). Together, these findings reconstruct the evolutionary origin of a previously unknown protein architecture and provide a framework for understanding the emergence of lineage-specific protein families in trypanosomatids.