Wnt-signalling pathways and microRNAs network in carcinogenesis: experimental and bioinformatics approaches

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 Wntsignalling 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 miRNAmediated 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.

Tumor-derived CXCL5 promotes human colorectal cancer metastasis through activation of the ERK/Elk-1/Snail and AKT/GSK3β/β-catenin pathways

“…GSK3β is a downstream effector of AKT, and pAKT can suppress the function of GSK3β by phosphorylating its serine residue [24]. GSK3β is a key component of the destruction complex that facilitates the phosphorylation of β-catenin in CRC [33]. Phosphorylated β-catenin can be recognized by β-TrCP, which ubiquitinates pβ-catenin, and the ubiquitinated pβ-catenin is then degraded by proteasomes [34].…”

Genome-wide Expression Profiling and Pathway Analysis in Cyclic Stretched Human Trabecular Meshwork Cells

“…Future studies will be needed to examine how this mechanical stress-induced Wnt signaling functions in glaucomatous TM cells or aged human TM cells. The Wnt signaling pathway could be regulated by several differentially expressed miRNAs, including miR-374a (44), miR-34a targeting p53 (45), let-7, and miR-31-5p (46). In summary, the interaction of Wnt signaling and miRNA regulation clearly contributes to the molecular response of human TM cells to cyclic mechanical stress.…”

Clinically Actionable Insights into Initial and Matched Recurrent Glioblastomas to Inform Novel Treatment Approaches

“…In this GBM cohort, amongst the BRCA2 variants were confirmed somatic mutations in haemangioblastoma (BRCA2 : COSM3753648, COSM5019704) [43], which is a rare, benign tumour that typically occurs in the cerebellum [3]. Many IDH WT tumours had alterations impacting WNT [59][60][61][62][63] signalling pathway genes (58%) including CREBBP(4), KLF4 (2) [64,65], TERT(2) [17], and APC(3) [66][67][68][69][70]; however, targeting this pathway is currently challenging. Initial IDH WT tumours also showed predicted pathogenic variation in NOTCH (11%) [71] and SHH (13%) pathways [72] including PTCH1 (PATCHED-1) and SMO (Smoothened) [73][74][75].…”