As important epigenetic regulators, microRNA regulate protein expression by triggering the degradation of target mRNA and/or by inhibiting their translation. Dysregulation of microRNA expression has been reported in several cancers, including colorectal cancer. In this study, microRNA-array differential analysis revealed strongly enhanced expression of miR-24-1-5p in the colon tissue of azoxymethane/dextran sulphate sodium-induced mice that were fed with black raspberry anthocyanins for 9 weeks. Overexpression of miR-24-1-5p in human colorectal cancer cells significantly repressed β-catenin expression, and simultaneously decreased cell proliferation, migration and survival. Furthermore, miR-24-1-5p could target β-catenin and trigger a negative regulatory loop for β-catenin and its downstream target genes. β-Catenin signalling is vital to the formation and progression of human colorectal cancer. The current findings therefore identified miR-24-1-5p as a potent regulator of β-catenin, and this may provide a novel chemopreventive and therapeutic strategy for β-catenin signalling-driven colorectal cancer.

Sea urchin embryos initiate cell specifications at the 16-cell stage by forming the mesomeres, macromeres and micromeres according to the relative position of the cells in the animal–vegetal axis. The most vegetal cells, micromeres, autonomously differentiate into skeletons and induce the neighbouring macromere cells to become mesoendoderm in the β-catenin-dependent Wnt8 signalling pathway. Although the underlying molecular mechanism for this progression is largely unknown, we have previously reported that the initial events might be triggered by the Ca2+ influxes through the egg-originated L-type Ca2+ channels distributed asymmetrically along the animal–vegetal axis and through the stretch-dependent Ca2+channels expressed specifically in the micromere at the 4th cleavage. In this communication, we have examined whether one of the earliest Ca2+ targets, protein kinase C (PKC), plays a role in cell specification upstream of β-catenin. To this end, we surveyed the expression pattern of β-catenin in early embryos in the presence or absence of the specific peptide inhibitor of Hemicentrotus pulcherrimus PKC (HpPKC-I). Unlike previous knowledge, we have found that the initial nuclear entrance of β-catenin does not take place in the micromeres, but in the macromeres at the 16-cell stage. Using the HpPKC-I, we have demonstrated further that PKC not only determines cell-specific nucleation of β-catenin, but also regulates a variety of cell specification events in the early sea urchin embryos by modulating the cell adhesion structures, actin dynamics, intracellular Ca2+ signalling, and the expression of key transcription factors.

The aim of this study was to describe and analyze the regulation and spatio-temporaldynamics of melanocyte migration in vitro and its coupling to celldivision and interaction with the matrix. The melanocyte lineage is particularlyinteresting because it is involved in both embryonic development andoncogenesis/metastasis (melanoma). Biological experiments were performed on two melanocytecell lines established from wild-type and β-catenin-transgenic mice(bcat*). The multi-functional β-catenin molecule is known to be able toregulate the transcription of various genes involved in cell proliferation and migration,particularly in the melanocyte lineage. We also investigated fibronectin, anextra-cellular matrix protein that binds integrins, thereby providing adhesion points forcells and encouraging migration. As the migration of individual cells were followed,automated methods were required for processing the large amount of data generated by thetime-lapse video-microscopy. A model-based approach for automated cell tracking wasevaluated on a sample by comparison with manual tracking. This method was found reliablein studying overall cell behaviour. Its application to all the observed sequences providedinsight into the factors affecting melanocyte migration in vitro:melanocytes of mutated form of β-catenin showed higher division rates andno contact inhibition of growth was induced by the resulting increase in cell density.However, cell density limited the amplitude of cell displacements, although their motilitywas less affected. The high fibronectin concentration bound to substratum promoted cellmigration and motility, the effect being more intense for wild-type cells than for cellswith β-catenin over-expression. During the division process, cellmigration speed increased rapidly then decreased slowly. Analyses of such data is expectedto lead both to biological answers and to a framework for a better modeling processes inthe future.

The anterior–posterior and dorsal–ventral progression of heart organogenesis is well illustrated by the patterning and activity of two members of different families of cell adhesion molecules: the calcium-dependent cadherins, specifically N-cadherin, and the extracellular matrix glycoproteins, fibronectin. N-cadherin by its binding to the intracellular molecule β-catenin and fibronectin by its binding to integrins at focal adhesion sites, are involved in regulation of gene expression by their association with the cytoskeleton and through signal transduction pathways. The ventral precardiac mesoderm cells epithelialize and become stably committed by the activation of these cell–matrix and intracellular signaling transduction pathways. Cross talk between the adhesion signaling pathways initiates the characteristic phenotypic changes associated with cardiomyocyte differentiation: electrical activity and organization of myofibrils. The development of both organ form and function occurs within a short interval thereafter. Mutations in any of the interacting molecules, or environmental insults affecting either of these signaling pathways, can result in embryonic lethality or fetuses born with severe heart defects. As an example, we have defined that exposure of the embryo temporally to lithium during an early sensitive developmental period affects a canonical Wnt pathway leading to β-catenin stabilization. Lithium exposure results in an anterior–posterior progression of severe cardiac defects.