Abstract
Simple SummaryIn cells possessing invasive or metastatic capabilities, several classes of proteins that are involved in the tethering of cells to their surroundings are altered. Loss of cell–cell and cell–matrix adhesions, proteolysis, and induction of angiogenesis are all processes that allow the development of cancer invasion and metastasis. Additionally, epithelial mesenchymal transition (EMT) is a major contributor to the aggressive behavior of cells responsible for invasive growth and metastasis. Here we cover the roles of a few microRNAs (miRNAs) on the molecules that have been shown to play a significant role in bladder cancer metastasis and angiogenesis. These miRNAs could be considered as therapeutic modalities or as diagnostic biomarkers in future research.Angiogenesis is the process of generating new capillaries from pre-existing blood vessels with a vital role in tumor growth and metastasis. MicroRNAs (miRNAs) are noncoding RNAs that exert post-transcriptional control of protein regulation. They participate in the development and progression of several cancers including bladder cancer (BLCA). In cancer tissue, changes in microRNA expression exhibit tissue specificity with high levels of stability and detectability. miRNAs are less vulnerable to degradation, making them novel targets for therapeutic approaches. A suitable means of targeting aberrant activated signal transduction pathways in carcinogenesis of BLCA is possibly through altering the expression of key miRNAs that regulate them, exerting a strong effect on signal transduction. Precaution must be taken, as the complexity of miRNA regulation might result in targeting several downstream tumor suppressors or oncogenes, enhancing the effect further. Since exosomes contain both mRNA and miRNA, they could therefore possibly be more effective in targeting a recipient cell if they deliver a specific miRNA to modify the recipient cell protein production and gene expression. In this review, we discuss the molecules that have been shown to play a significant role in BLCA tumor development. We also discuss the roles of various miRNAs in BLCA angiogenesis and metastasis. Advances in the management of metastatic BLCA have been limited; miRNA mimics and molecules targeted at miRNAs (anti-miRs) as well as exosomes could serve as therapeutic modalities or as diagnostic biomarkers.
Highlights
Bladder cancer (BLCA) is the most malignant disease of the urinary tract with variable metastatic potential
In BLCA, tumor staging presents the depth of bladder wall invasion, with stages Ta and T1 where the tumors are isolated to the urothelium and lamina propria, respectively, considered as NMIBC, while stages T2, T3, and T4, which has invaded the muscle as MIBC
The studies summarized in this review clearly indicate that in bladder cancer, microRNAs are involved in the regulation of metastasis and angiogenesis
Summary
Bladder cancer (BLCA) is the most malignant disease of the urinary tract with variable metastatic potential. Over 40 miRNAs are involved in urological cancer, and a number of them target common carcinogenic pathways They regulate cell proliferation, EMT, tumor invasion pathways, angiogenic signaling, and control the expression of more than a third of human genes [11]. Suggested that since cancer cells can reside in various phenotypic states along the EMT spectrum, and the fact that they can transition dynamically between the epithelial and mesenchymal phenotypes manifests their ability to survive and seed metastatic deposits, providing cancer cells with tumor initiating potential and the ability to maintain phenotypic plasticity [23]
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