MicroRNA regulons in tumor microenvironment

Abstract

Cancer initiation and progression are defined by the behavior of cancer cells per se and the development of tumor tissues, both of which are modulated by crosstalk between cancer cells and the surrounding microenvironment. Advances in cancer research have highlighted the significance of constant evolution of the tumor microenvironment, leading to tumor formation, metastasis and refractoriness to therapy. MicroRNAs (miRNAs) are small non-coding RNAs that function as major players of posttranscriptional gene regulation in diverse biological processes. They function as both tumor suppressors and promoters in many aspects of the autonomous behavior of cancer cells. Theoretically, dysfunction in the gene regulatory networks of cancer cells is one of the major driving forces for alterations of ostensibly normal surrounding cells. In this context, the core targets of miRNAs, termed miRNA regulons, are currently being expanded to include various modulators of the tumor microenvironment. Recent advances have highlighted two important roles played by miRNAs in the evolution of tumor microenvironments: miRNAs in tumor cells transform the microenvironment via non-cell-autonomous mechanisms, and miRNAs in neighboring cells stabilize cancer hallmark traits. These observations epitomize the distal and proximal functions of miRNAs in tumor microenvironments, respectively. Such regulation by miRNAs affects tumor angiogenesis, immune invasion and tumor-stromal interactions. This review summarizes recent findings on the mechanisms of miRNA-mediated regulation of tumor microenvironments, with a perspective on the design of therapeutic interventions.

Circulating microRNAs associated with prolonged overall survival in lung cancer patients treated with nivolumab

“…They are stable, seem to be protected from degradation and can easily be analyzed, and hence are attractive biomarker candidates [15]. It has also been shown that tumor-derived microRNAs can modulate cells in the tumor microenvironment [16], and may be essential in the cross talk between tumor cells and immune cells. Specific microRNAs are associated with immune cells active in tumor stroma and suggested to mediate changes in the tumor microenvironment [17].…”

Brain Metastasis of Breast Cancer: Crossing the Blood-brain Barrier

“…Recent work has shown that miRNAs of cancer cells modulate the tumor microenvironment, such as tumor angiogenesis, tumor immune invasion, and tumor-stromal interactions [40]. In breast cancer cells, miR-9 can target and downregulate E-cadherin, which in turn upregulates VEGF expression, leading to the increase of cell motility and invasiveness [41].…”

Reciprocal regulation between microRNAs and epigenetic machinery in colorectal cancer

“…Despite the use of various detection methods, including microarray, sequencing, real-time polymerase chain reaction-based approaches and in situ hybridisation, a high consistency of miRNA expression profiles exists among these studies, which indicates that these miRNAs are essential elements in cancer progression (16)(17)(18)(19).…”