Review Article

The Role of miRNAs as Key Regulators in the Neoplastic Microenvironment

Figure 1

Validated miRNAs and their gene targets in the microenvironment. In carcinoma cells, the loss of miR-17/20 is involved in heterotypic signaling through the upregulation of cytokines IL-8 and CXCL-1 as well as plasminogen activators CK8 and α-ENO. In the ECM, decreased amounts of miR-29c are found to result in an increase in collagens and laminin leading to alteration in ECM composition conducive to invasion and migration. In addition, miR-146b is also decreased resulting in increased activity of MMP16 in ECM degradation. In contrast, miR-21 levels are elevated resulting in inhibition of RECK and TIMP3, important metalloproteinase inhibitors. In the CAF, although multiple miRNAs are differentially expressed, to date only a decrease in miR-31 has been validated to be directly involved in an upregulation of SATB2 resulting in increased invasiveness and migration.
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