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Desmosomes play a key role in the regulation of cell adhesion and signaling. Dysregulation of the desmosome complex is associated with the loss of epithelial cell polarity and disorganized tissue architecture typical of colorectal cancer (CRC). The aim of this study was to investigate and characterize the effect of miR-195-5p on desmosomal junction regulation in CRC. In detail, we proposed to investigate the deregulation of miR-195-5p and JUP, a gene target that encodes a desmosome component in CRC patients. JUP closely interacts with desmosomal cadherins, and downstream, it regulates several intracellular transduction factors. We restored the miR-195-5p levels by transient transfection in colonic epithelial cells to examine the effects of miR-195-5p on JUP mRNA and protein expression. The JUP regulation by miR-195-5p, in turn, determined a modulation of desmosome cadherins (Desmoglein 2 and Desmocollin 2). Furthermore, we focused on whether the miR-195-5p gain of function was also able to modulate the expression of key components of Wnt signaling, such as NLK, LEF1 and Cyclin D1. In conclusion, we have identified a novel mechanism controlled by miR-195-5p in the regulation of adhesive junctions, suggesting its potential clinical relevance for future miRNA-based therapy in CRC. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer types, and it is associated with a 5-year survival rate of <10% due to limited early detection methods and ineffective therapeutic options. Thus, an improved understanding of the mechanisms involved in the early stages of PDAC tumorigenesis is crucial in order to identify potential novel diagnostic and therapeutic targets. The most common signalling aberrations in PDAC occur in the Wnt/Notch signalling pathway, as well as within the epidermal growth factor receptor (EGFR) pathway and its associated ligands, EGF and transforming growth factor-β. In addition, the RAS family of oncogenes, which act downstream of EGFR, are found mutated in most pancreatic cancer samples. Plakoglobin, a component of the EGFR signalling pathway, serves an important role in normal cell adhesion; however, its role in PDAC is largely unknown. The present study used transcriptome sequencing and focussed proteome microarrays to identify dysregulated genes and proteins in PDAC. The presence of upregulated plakoglobin expression levels was identified as a distinguishing feature between the PDAC microenvironment and normal pancreatic tissue. Furthermore, plakoglobin was demonstrated to be associated with the differential upregulation of the PI3K/AKT and MAPK signalling pathways in the tumour microenvironment, which suggested that it may serve an important role in PDAC tumourigenesis. [ABSTRACT FROM AUTHOR]