Regulators at Every Step—How microRNAs Drive Tumor Cell Invasiveness and Metastasis

SIMPLE SUMMARY: Tumor cell invasiveness and metastasis are key processes in cancer progression and are composed of many steps. All of them are regulated by multiple microRNAs that either promote or suppress tumor progression. Multiple studies demonstrated that microRNAs target the mRNAs of multiple genes involved in the regulation of cell motility, local invasion, and metastatic niche formation. Thus, microRNAs are promising biomarkers and therapeutic targets in oncology. ABSTRACT: Tumor cell invasiveness and metastasis are the main causes of mortality in cancer. Tumor progression is composed of many steps, including primary tumor growth, local invasion, intravasation, survival in the circulation, pre-metastatic niche formation, and metastasis. All these steps are strictly controlled by microRNAs (miRNAs), small non-coding RNA that regulate gene expression at the post-transcriptional level. miRNAs can act as oncomiRs that promote tumor cell invasion and metastasis or as tumor suppressor miRNAs that inhibit tumor progression. These miRNAs regulate the actin cytoskeleton, the expression of extracellular matrix (ECM) receptors including integrins and ECM-remodeling enzymes comprising matrix metalloproteinases (MMPs), and regulate epithelial–mesenchymal transition (EMT), hence modulating cell migration and invasiveness. Moreover, miRNAs regulate angiogenesis, the formation of a pre-metastatic niche, and metastasis. Thus, miRNAs are biomarkers of metastases as well as promising targets of therapy. In this review, we comprehensively describe the role of various miRNAs in tumor cell migration, invasion, and metastasis.