Functional roles of microRNAs in vasculogenic mimicry and resistance to therapy in human cancers: an update

ABSTRACT

Introduction

Vasculogenic mimicry (VM) alludes to the ability of cancer cells to organize on three-dimensional channel-like structures to obtain nutrients and oxygen. This mechanism confers an aggressive phenotype, metastatic potential, and resistance to chemotherapy resulting in a poor prognosis. Recent studies have been focused on the identification of microRNAs (miRNAs) that regulate the VM representing potential therapeutic targets in cancer.

Areas covered

An overview of the roles of miRNAs on VM development and their functional relationships with tumor microenvironment. The functions of cancer stem-like cells in VM, and resistance to therapy are also discussed. Moreover, the modulation of VM by natural compounds is explored. The clinical significance of deregulated miRNAs as potential therapeutic targets in tumors showing VM is further highlighted.

Expert opinion

The miRNAs are regulators of protein-encoding genes involved in VM; however, their specific expression signatures with clinical value in large cohorts of patients have not been established yet. We considered that genomic profiling of miRNAs could be useful to define some hallmarks of tumors such as stemness, drug resistance, and VM in cancer patients. However, additional studies are needed to establish the relevant role of miRNAs as effective therapeutic targets in tumors that have developed VM.

KEYWORDS:

• Vasculogenic mimicry
• microRNAs
• cancer stem-like cells
• epithelial-mesenchymal-transition
• therapy

Article highlights

• The low tissular oxygen concentration results in changes in intracellular pH, modifying signaling and metabolic pathways of cancer cells, which favor the vasculogenic mimicry (VM) formation.

• HIF-1a is the main protagonist in the regulation of molecules such as VE-cadherin, EphA2, LN5γ2, MMPs, VEGF, STAT3, Bcl-2, activating signaling pathways that favor the formation of 3D channel-like structures.

• In most types of cancer, microRNAs regulate the VM formation and metastasis.

• VM is preferably carried out in cancer stem-like cells and due to their high plasticity and dominant quiescence state, the conventional cancer therapies are not effective, resulting in a poor prognosis in patients.

• Polyphenols exhibit diverse biological effects such as antioxidants and anti-tumor, increasing the effects of chemotherapeutic agents through the regulation of miRNAs associated with VM.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

We thank the Universidad Autonoma de la Ciudad de Mexico and CONAHCYT for support.

Additional information

Funding

This research was funded by Consejo Nacional de Humanidades Ciencia y Tecnologia (CONAHCYT), Mexico, Grant FOSSSIS A3-S-33674