MicroRNAs (miRNAs) are small (around 22 nt) endogenous non-coding RNAs which regulate gene expression by base-pairing to the 3′-UTR of the target mRNA, causing translational repression or mRNA degradation. Recently, miRNAs have been shown to regulate cancer metastasis by virtue of their ability to co-ordinately repress multiple target genes. Epithelial-mesenchymal transition (EMT), which is characterized by repression of E-cadherin expression, and increased cell mobility, plays a very important role in cancer metastasis and fibrosis development. Recent evidence suggests that microRNA-30 (miR-30) acts as an antifibrotic agent and reduces tumor weight in animal models. In the present study, we have identified that the miR-30 family of miRNAs may function as anti-metastatic miRNAs by inhibiting EMT. We have studied the expression of miR-30 in various NSCLC cell lines and found that miR-30 expression is inversely proportional to the invasive capabilities of the cells. Correspondingly, all ‘mir-30 high’ cells are E-cadherin (epithelial marker) positive and N-cadherin (mesenchymal marker) negative, and vice-versa. ‘miR-30 low’ cell lines displayed several fold higher migratory and invasive abilities when compared with ‘miR-30 high’ cell lines. Similarly, in a chicken embryonic metastasis assay, we found that the number of metastasizing cells to lungs and livers of developing chicken was significantly reduced when miR-30 was over-expressed in ‘miR-30 low’ cells compared with mock-transfected cells. Over-expression of miR-30 also inhibited TGF-beta induced EMT in ‘miR-30 low’ cells, confirming the role of miR-30 in EMT inhibition. Search for miR-30 targets, that can modulate E-cadherin expression, using web based target analysis tools, have identified that Snail, which induces EMT primarily via transcriptional repression of E-cadherin, is a putative target of miR-30. Luciferase and Western blotting experiments have confirmed that miR-30 targets Snail. Finally, we have screened the expression of miR-30 in 47 consecutive NSCLC patients and found that miR-30 is down-regulated in tumours of about 80% of patients compared with their corresponding normal tissue. Collectively, these observations suggest that members of miR-30 are down regulated in non-small cell lung cancer, and inhibit EMT by targeting Snail.

Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2085.