Abstract 2894: Integrated bioinformatic analysis to elucidate molecular mechanisms associated with reversal of osteosarcoma malignancy induced by CD99

• Published in: Cancer research (Chicago, Ill.) Vol. 73; no. 8_Supplement; p. 2894
• Main Authors: Sciandra, Marika, Grilli, Andrea, Marino, Maria Teresa, Manara, Maria Cristina, Picci, Piero, Scotlandi, Katia
• Format: Journal Article
• Language: English
• Published: 15.04.2013
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2013-2894

Abstract Introduction: CD99 is a transmembrane glycoprotein which is physiologically involved in several biological processes, such as cell migration, adhesion, and differentiation. High levels of CD99 have been reported in mesenchymal stem cells and osteoblasts. In contrast, the molecule has been shown to be absent in osteosarcoma (OS), in which it acts as a tumour suppressor. The molecular mechanisms responsible for its functions are however still poorly defined. In this study we used bioinformatic studies to integrate gene expression and miRNA data to identify crucial mediators. Methods: Forced expression of CD99 was stably induced in Saos-2 OS cell line. Microarray analyses of gene or miRNA expression were performed and integrated by using different bioinformatic approaches. TargetScan, Miranda, Diana-microT and PicTar prediction databases were used to identify miRNA targets. Results: CD99-overexpressing cells displayed a massive down-regulation of gene expression. Only 19 probes were found to be significantly up-regulated in CD99 transfectants compared to parental cells. In contrast, 231 probes were found to be down-regulated, thus suggesting gene modulation by epigenetic mechanisms. We thus examined miRNA profile of these cells. A significant up-regulation of miR-1225-3p, miR-1238, miR-1305, miR-191*, miR-34a, and miR-425* was observed in CD99 overexpressing cells. Enrichment analyses pointed out an involvement of TGFβ signalling. Interestingly, SMAD-2 and -4, which emerged as targets of miR-34a, were among the main down-modulated genes. miR34 mimics confirmed the association between miR34a and SMAD-4. Functional studies are on-going to establish associations with osteosarcoma malignancy. Conclusions: Besides inhibiting osteosarcoma malignancy, CD99 expression in osteosarcoma cells determines massive gene expression repression, likely due to changes in miRNA profile. Up-regulation of miR-34a together with down-regulation of TGFβ signalling mediators seem to be critical players. Studies are granted by AIRC 10452 and Ministry Health RF-2009 to KS. Citation Format: Marika Sciandra, Andrea Grilli, Maria Teresa Marino, Maria Cristina Manara, Piero Picci, Katia Scotlandi. Integrated bioinformatic analysis to elucidate molecular mechanisms associated with reversal of osteosarcoma malignancy induced by CD99. [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 2894. doi:10.1158/1538-7445.AM2013-2894