Presentation Abstract

Abstract Number: 2022
Presentation Title: The WAVE3-dependent cancer cell invasion is regulated by miR-31 during cancer progression and metastasis
Presentation Time: Monday, Apr 19, 2010, 2:00 PM - 5:00 PM
Location: Exhibit Hall A-C, Poster Section 3
Poster Section: 3
Poster Board Number: 3
Author Block: Khalid Sossey-Alaoui. Cleveland Clinic Lerner Research Institute, Cleveland, OH
Abstract Body: MicroRNAs are small non-coding RNAs that are directly involved in the regulation of gene expression by either translational repression or degradation of target mRNAs. Because of the high level of conservation of the target motifs, known as seed sequences, within the 3′-untranslated regions (UTR), a single microRNA can regulate numerous target genes simultaneously, providing a mechanism for this class of RNAs to serve as master regulators of gene expression. Loss of expression of miR-31 has recently been suggested to be associated with cancer progression and metastasis (1).Our previous studies reported a very significant correlation between the expression levels of WAVE3, an actin cytoskeleton remodeling protein, and advanced stages of breast cancer, clearly supporting the function of WAVE3 as a metastasis promoter protein (2). Here we show that the activity of WAVE3 to promote cancer cell invasion is regulated by miR-31 microRNA. We also show a clear inverse correlation between expression levels of WAVE3 and miR-31in invasive versus non-invasive cancer cells. miR-31 directly targets the 3’-UTR of the WAVE3 mRNA and inhibits its expression in the invasive cancer cells. The miR-31-mediated down-regulation of WAVE3 results in a significant reduction in the invasive phenotype of cancer cells, which is specific to the loss of WAVE3 expression since re-expression of a miR-31-resistant form of WAVE3 reverses miR-31-mediated inhibition of cancer cell invasion. We finally report a correlation between the expression levels of WAVE3 and miR-31 in non-invasive vs highly invasive primary human breast cancer tumors. In conclusion, a novel mechanism for the regulation of WAVE3 expression in cancer cells has been identified, which controls the invasive properties of cancer cells. The present study also identifies a critical role for WAVE3, downstream of miR-31, in at least one of the multiple steps that govern the invasion-metastasis cascade.
References:
1-Valastyan et al., A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis. Cell 137:1032-1046. 2009.
2-Sossey-Alaoui et al., Down-regulation of WAVE3, a metastasis promoter gene, inhibits invasion and metastasis of breast cancer cells. Am J Pathol. 170:2112-2121. 2007.