MicroRNA‐183 regulates Ezrin expression in lung cancer cells

Abstract

Lung cancer is the leading cause of cancer death. However, the mechanism of lung cancer relapse and metastasis has been poorly elucidated. Recent researches have addressed the role of MicroRNAs (miRNAs) in mediating tumor metastasis. In the present study, we identified microRNA-183 (miR-183) as a potential metastasis-inhibitor. Expression level of miR-183 was reversely correlated with the metastatic potential of lung cancer cells. Furthermore, over-expression of miR-183 inhibited migration and invasion of lung cancer cells. Mechanistically, we identified VIL2-coding-protein Ezrin as a bona fide target of miR-183. We also found that miR-183 could regulate the expression of other genes involved in migration and invasion. Taken together, our findings demonstrated a new role and regulatory mechanism of miR-183 in controlling cancer metastasis.

Targeting of Integrin β1 and Kinesin 2α by MicroRNA 183

“…These effects on migration and invasion were prevented by expression of ITGB1 lacking the 3Ј-UTR, indicating that they were mediated, at least in part, by inhibition of ITGB1. The inhibition of migration and invasion of HeLa cells through direct targeting of ITGB1 is consistent with the anti-metastatic role proposed for miR-183 by Wang et al (5) and provides an additional mechanism that might contribute to the regulation of cancer invasiveness through the inhibition of ITGB1. A large body of experimental evidence supports an essential role for ITGB1 during tumor induction and invasiveness (11)(12)(13)(14)(15).…”

“…MiR-183 has been found to be up-regulated in the retina of a mouse model of retinitis pigmentosa (1) as well as in colorectal cancer (2)(3)(4). Despite its up-regulation in colorectal carcinoma cells, it has been proposed that miR-183 may inhibit the invasiveness of certain cancer cells (5). This potential anti-metastatic role of miR-183 is supported by the observations that miR-183 expression is inversely correlated with the metastatic potential of lung cancer cells.…”

“…Its ectopic expression in highly metastatic cells can inhibit cell migration and invasion. Furthermore, the expression of the VIL2 coding protein Ezrin, which is known to be functionally important in cancer progression, has been demonstrated to be post-transcriptionally regulated by miR-183 (5).…”

“…Specifically, it has been proposed that miR-183 could contribute to reinforcing the post-mitotic differentiated state of hair cells (6). However, functional data for this miRNA is currently limited to the work by Wang et al (5) on lung cancer cells.…”

The microRNA network and tumor metastasis

“…Anti-metastatic miRNAs regulate tumor metastasis Wang et al (2008) identified miR-183 as a negative regulator of lung cancer metastasis by screening with a miRNA array. The target gene, Ezrin, which was confirmed by luciferase reporter gene assay, has a role in controlling the actin cytoskeleton, cell adhesion and motility.…”