MicroRNAs — the micro steering wheel of tumour metastases

Abstract

Recently, microRNAs (miRNAs) have been discovered to have a role in metastasis. Here we describe how miRNAs are involved in advanced stages of tumour progression, stressing their roles as metastasis activators or suppressors, and discuss their possible use in the clinic as predictive markers and as therapeutic strategies for patients with metastases. Furthermore, we develop the concept that the same miRNAs could be involved both in the cancer stem cell phenotype and in the ability of specific cancer cells to produce metastases, thus representing a mechanistic link between the initial and the final steps of tumorigenesis.

Control of EVI-1 oncogene expression in metastatic breast cancer cells through microRNA miR-22

“…Studies on miR-126 show the context-specific actions in tumorigenesis. In breast cancer, loss of miR-126 leads to increased cell proliferation without effects on motility, whereas in non-small cell lung cancers, loss of miR-126 leads to increased motility without effects on proliferation (Nicoloso et al, 2009). Other such miRNAs include miR-29c involvement in modulating the tumor microenvironment and miR-146 modulation of amoeboid motility (Friedl and Wolf, 2003; Ramaswamy et al, 2003).…”

“…At the center of these investigations are microRNAs (miRNAs). These small non-coding RNAs are now thought to be one of the major regulators of gene expression (Nicoloso et al, 2009).…”

Genetic modulation of the Let-7 microRNA binding to KRAS 3′-untranslated region and survival of metastatic colorectal cancer patients treated with salvage cetuximab–irinotecan

“…24,25 In this perspective, there is the possibility that more than one miRNA is implicated and exploited in the control of the RAS pathway. 26,27 Future studies should also analyze the effect of Let-7 and its genetic modulation in patients with early disease and in patients treated with chemotherapy.…”

Hypoxia and RAS-signaling pathways converge on, and cooperatively downregulate, the RECK tumor-suppressor protein through microRNAs

“…Recent studies indicate that cancer cells show characteristic microRNA (miRNA) expression profiles, which, at least in part, reflect the upregulation of oncogenic miRNAs (targeting tumor-suppressor genes) and downregulation of tumor-suppressor miRNAs (targeting oncogenes), which lead to misbehavior of cancer cells, including invasion and metastasis (Calin and Croce, 2006;Ma and Weinberg, 2008;Nicoloso et al, 2009). It is now important to clarify their clinically relevant targets, their functional relationships and the mechanisms of their altered expression.…”