, Volume 89, Issue 5, pp 445-457

MicroRNAs (miRNAs) in cancer invasion and metastasis: therapeutic approaches based on metastasis-related miRNAs

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Abstract

The management of tumor cell invasion and metastasis is instrumental in cancer therapy, since metastases are the prime reason for cancer patient mortality. Various cellular mechanisms and underlying molecular pathways relevant for metastasis have been identified so far, providing a basis for antimetastatic drugs. MicroRNAs (miRNAs) are highly conserved, small noncoding RNA molecules that have been shown to regulate various cellular processes by interfering with protein expression through posttranscriptional repression or mRNA degradation. More importantly, beyond their roles in physiological processes, many miRNAs are aberrantly expressed in various pathologies including cancer and regulate tumor- and metastasis-associated genes. Their pivotal role in metastasis has emerged only recently. After an introduction into the mechanisms of miRNA action, this review article describes the roles of miRNAs in cancer invasion and metastasis. Various miRNAs are discussed with regard to their upstream regulators, downstream target genes, and pro-/antimetastatic effects. A table provides a comprehensive overview of miRNAs that are misregulated/relevant in metastasis and the current knowledge regarding their underlying molecular effects. Furthermore, therapeutic approaches based on miRNAs, either as drugs or as therapeutic targets, are described prior to the discussion of the delivery of miRNA-based therapeutics as novel strategy in antimetastatic treatment.