Abstract 3070: MicroRNA-155 directly targets PDCD4 and activates BIC promoter through AP-1 dependent transcription to replenish miR-155 expression in SAS cells

Abstract

Abstract Pdcd4 (programmed cell death 4) has been demonstrated to be a tumor suppressor gene and is expressed at higher levels during apoptosis. PDCD4 is down regulated in a subset of oral cancers (tongue and buccal cavity) and an association between its down-regulation by miR-21 and tumorigenesis and invasion in oral carcinoma has been demonstrated. In this study we show that miR-155 directly targets PDCD4 in SAS (tongue squamous carcinoma) cells. We demonstrate a positive feedback loop between miR-155 expression and AP-1 dependent transcription through the down regulation of PDCD4. Analysis of miR-155 promoter (BIC) showed the presence of NF-κB and AP-1 (c-Jun and c-Fos) transcription factor binding sites and PDCD4 is known to inhibit AP-1 dependent transcription. Ectopic expression of PDCD4 in SAS cells drastically reduced the BIC promoter activity via inhibition of AP-1 dependent transcription and down regulated the levels of miR-155. We also generated the Lentiviral based miR-155 sponge stable cells to down regulate miR-155 in SAS cells, and found an increase in PDCD4 protein levels. The activity of BIC promoter was relatively low in miR-155 sponge stable cells compared to control sponge stable cells as analyzed by a dual luciferase reporter assay. We have also seen the reduced rate of proliferation in miR-155 sponge stable cells compared to control sponge stable cells. Thus our data show that miR-155 directly targets PDCD4 and consequently activates AP-1 dependent transcription in BIC promoter and increasing the levels of miR-155. Citation Format: shabir A. zargar, Devarajan Karunagaran. MicroRNA-155 directly targets PDCD4 and activates BIC promoter through AP-1 dependent transcription to replenish miR-155 expression in SAS cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3070. doi:10.1158/1538-7445.AM2015-3070