Abstract 5283: Regulation of tetraspanins CD151 and CD9 by micro-RNA in breast and prostate cancers.

Abstract

Abstract Rationale: Tetraspanins are involved in modulating various cellular functions related to cancer progression, such as cell-cell adhesion, migration and signalling. The tetraspanin CD151 (pro-metastatic) is typically over-expressed in cancers, whereas CD9 (metastasis suppressor) is generally under-expressed in cancers. Increased CD151 protein expression in breast and prostate cancers significantly correlates with poor patient outcomes, whereas high CD9 protein expression in these cancers is associated with good patient prognosis. However, progress in developing CD151 and CD9 as prognostic biomarkers and therapeutic targets is hampered by a lack of understanding of the mechanisms controlling altered CD151 and CD9 protein expression in cancers. Objective: miRNAs, which are small non-coding RNAs involved in post-transcriptional control, are known to be dysregulated in breast and prostate cancers. Bioinformatics analysis has identified around 250 miRNA, which are predicted to bind CD151 or CD9, thus we aim to investigate if miRNAs are able to regulate the expression of CD151 and CD9 in vitro using a range of breast and prostate cancer cell lines. Methods and Results: Using a dual luciferase reporter assay the level of protein expression regulation via CD151 or CD9 3’UTR, where miRNA generally bind their targets, was determined in 13 breast and prostate cell lines. This analysis showed that the amount of targeting of CD151 and CD9 varied across these cell lines indicating a role for miRNA. Analysis of miRNA expression in normal and cancerous cell lines using miRNA expression arrays and qPCR has confirmed that some miRNAs which are predicted to target CD9 such as miR-25 are up-regulated in many prostate and breast cancer cell lines compared to non-tumourigenic cells. Conversely, miRNA were identified with different expression levels that are predicted to target CD151. To determine whether these miRNAs directly regulate CD151 or CD9, a dual luciferase 3’UTR reporter assay encompassing specific miRNA mimics is being used. Conclusion: Altered miRNA expression is one way in which prostate and breast cancer cells might alter tetraspanin protein expression to allow cancer progression and metastasis. Citation Format: Danielle R. Bond, Murray Cairns, Leonie K. Ashman, Judith Weidenhofer. Regulation of tetraspanins CD151 and CD9 by micro-RNA in breast and prostate cancers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5283. doi:10.1158/1538-7445.AM2013-5283 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.