microRNAs in the tumor microenvironment: solving the riddle for a better diagnostics

Abstract

miRNAs are small noncoding RNAs with gene regulatory functions, frequently dysregulated in human cancers. Specific signatures of differentially expressed miRNAs can be used in the diagnosis of cancer and in some cases harbor prognostic implications. The biology of cancer is dictated not only by cancer cells but also by the surrounding tumor microenvironment. In particular, the role of miRNAs within the tumor microenvironment is emerging as of paramount importance. This review will focus on the current knowledge of the role of miRNAs and both cellular and stromal components of the tumor microenvironment. We will also discuss more recent findings, showing that miRNAs can be found inside of exosomes and mediate the cross-talk between cancer cells and surrounding cells, leading to the discovery of new fascinating molecular mechanisms leading to a better understanding of the cancer ‘niche’ and how these noncoding RNAs can become very promising diagnostic molecules.

Keywords::

• biomarker
• exosomes
• extracellular matrix
• immunity
• inflammation
• miRNA
• stroma
• toll-like receptor
• tumor microenvironment

Financial & competing interests disclosure

M Fabbri is a St. Baldrick Foundation’s scholar and is supported by the Pablove Foundation, the Saban Research Institute Research Career Development Award, the Southern California Clinical and Translational Science Institute (SC CTSI), the Jean Perkins Foundation, the Nautica Malibu Triathlon Funds, the National Cancer Institute award number P30CA014089, the Hugh and Audy Lou Colvin Foundation, and by a Shirley McKernan donation. The authors have no other 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 apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• miRNAs play a central role in human carcinogenesis.

• miRNAs can be detected in all human fluids and can be effectively used as biomarkers for cancer diagnosis, prognosis and prediction of response to treatments.

• miRNAs affect the biology of cells of the tumor microenvironment.

• miRNAs modulate the biology of the stroma of the tumor microenvironment.

• miRNAs are secreted by cancer cells within microvesicles called exosomes.

• Exosomic miRNAs can be transferred from cancer cells to surrounding cells where they are functional and can silence target genes.

• Exosomic miRNAs can bind to toll-like receptor 8 and trigger a protumoral inflammatory response.

• A better understanding of the relationship between systemic miRNAs and miRNAs within the tumor microenvironment is of utmost importance to develop better miRNA-based cancer diagnostic biomarkers.

Notes