Abstract
MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression by suppressing translation or facilitating mRNA decay. Differential expression of miRNAs is involved in the pathogenesis of several diseases including cancer. Here, we investigated the role of-miR-24-3p as a downregulated miRNA in metastatic cancer. miR-24-3p was decreased in metastatic cancer and lower expression of miR-24-3p was related to poor survival of cancer patients. Consistently, ectopic expression of miR-24-3p suppressed the cell migration, invasion, and proliferation of MCF7, Hep3B, B16F10, SK-Hep1, and PC-3 cells by directly targeting p130Cas. Stable expression of p130Cas restored miR-24-3p-mediated inhibition of cell migration and invasion. These results suggest that miR-24-3p functions as a tumor suppressor and the miR-24-3p/p130Cas axis is a novel factor of cancer progression by regulating cell migration and invasion.
Highlights
MicroRNAs are small non-coding RNAs that negatively regulate gene expression by suppressing translation or facilitating mRNA decay
We further investigated the relative level of miR-24-3p between primary tumors without metastasis (Non-Meta) and metastatic tumors (Meta) and found that miR-24-3p was significantly downregulated in metastatic tumors (Fig. 1B)
To test whether a lower level of miR-24-3p is related to an increase in the metastatic potential of cancer cells, we investigated cell migration and invasion in five different types of cancer cells, human breast adenocarcinoma MCF7 and human hepatocellular carcinoma Hep3B and SK-Hep[1] cells, human prostate cancer PC-3 cells, and mouse melanoma B16F10 cells after ectopic expression of miR-24-3p
Summary
MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression by suppressing translation or facilitating mRNA decay. MiRNAs suppress target gene expression by promoting mRNA degradation or inhibiting translation, thereby affecting a wide spectrum of biological processes such as development, differentiation, proliferation, and death[6,7]. It has been reported that miRNAs function as oncogenes or tumor suppressors, and aberrant expression of miRNAs is related to cancer progression via the regulation of cell growth, drug resistance, and metastasis[8,9,10]. MiRNAs were involved in the regulation of p130Cas expression; miR-362-3p and miR-329 suppressed cancer progression by targeting p130Cas[20]. We investigated the role of miR-24-3p, one of the downregulated miRNAs in metastatic cancers, in the regulation of cell migration and invasion. Ectopic expression of miR-24-3p inhibited cell migration, www.nature.com/scientificreports/
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