Abstract
Over the past few years, microRNAs (miRNAs) have not only emerged as integral regulators of gene expression at the post-transcriptional level but also respond to signalling molecules to affect cell function(s). miRNAs crosstalk with a variety of the key cellular signalling networks such as Wnt, transforming growth factor-β and Notch, control stem cell activity in maintaining tissue homeostasis, while if dysregulated contributes to the initiation and progression of cancer. Herein, we overview the molecular mechanism(s) underlying the crosstalk between Wnt-signalling components (canonical and non-canonical) and miRNAs, as well as changes in the miRNA/Wnt-signalling components observed in the different forms of cancer. Furthermore, the fundamental understanding of miRNA-mediated regulation of Wnt-signalling pathway and vice versa has been significantly improved by high-throughput genomics and bioinformatics technologies. Whilst, these approaches have identified a number of specific miRNA(s) that function as oncogenes or tumour suppressors, additional analyses will be necessary to fully unravel the links among conserved cellular signalling pathways and miRNAs and their potential associated components in cancer, thereby creating therapeutic avenues against tumours. Hence, we also discuss the current challenges associated with Wnt-signalling/miRNAs complex and the analysis using the biomedical experimental and bioinformatics approaches.
Highlights
BackgroundThe Wnt pathway is a highly regulated signalling pathway that controls numerous stages of animal development and tissue homeostasis
Canonical Wnt-signalling The canonical Wnt-signalling cascade refers to the transduction of series of signals mediated via the interaction of specific Wnt ligands with their target receptor resulting in the accumulation of β-catenin (Fig. 1a)
Not used for the validation of miRNA/Wnt-signalling network in cancer, patient-derived induced pluripotent stem cells (iPSC) approaches [203], have been employed in other studies for Conclusions the application of bioinformatics in the elucidation of the miRNAs-mediated regulation of Wntsignalling is extremely beneficial (Fig. 5), in the area of cancer research, the significant challenges that remain still signify the usefulness of experimental approaches for the analysis and validation of bioinformatics data
Summary
The Wnt pathway is a highly regulated signalling pathway that controls numerous stages of animal development and tissue homeostasis. The Wnt proteins comprise a highly conserved and diverse family of genes found in humans, mice, Xenopus, Zebrafish and Drosophila [1] The pathway is closely regulated at both transcriptional-level regulations to post-translational modification; aberrant Wnt activity often results in developmental disorders and diseases including but not limited to cancer [2,3,4]. Recent advances in biomedical research have allowed experimental and bioinformatics approaches to identify short noncoding RNAs such as microRNAs (miRNAs) as regulators of components of the Wnt-signalling pathways and vice versa. Both miRNAs and Wnt-signalling pathways form a network involved in the regulation of key biological processes
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