Abstract 2075: MicroRNA-21 expression levels are accompanied by respective alterations in pdcd4 protein levels in non-small cell lung cancer

Abstract

Abstract Introduction: MicroRNA-21 is a well characterized cancer associated miRNA as it has been found overexpressed in nine types of solid tumors and in other malignancies. The role of miR-21 is related with diverse carcinogenesis processes. The downregulation of tumor suppressor genes through the overexpression of miR-21 has been demonstrated for PTEN and TPM1. Very recently, it was revealed that programmed cell death 4 (PDCD4) is another target of miR-21 in colon and breast cancer cell lines. As it has not been yet studied the correlation between miR-21 and PDCD4 levels in clinical samples, we conducted the present study to investigate the possible regulation of pdcd4 protein levels by mature miR-21. Materials and Methods: Forty pairs of NSCLC fresh-frozen tissues and their corresponding noncancerous tissues were analyzed for the expression of mature miR-21 using quantitative real-time RT-PCR, as previously described (Markou et al., 2008). In parallel, PDCD4 protein levels were evaluated by immunohistochemistry. Deparaffinized sections cut from paraffin-embedded tissue samples were stained with a specific anti-PDCD4 antibody (1:100 dilution) (Ozaki et al., 2006) using HRP DAB kit (DAKO) for the detection. The tumor types and stages were determined according to the WHO classification. All samples were analyzed histologically to access the amount of tumor component (at least 70% of tumor cells) and the quality of material. Results: Among the 40 NSCLC tissue specimens studied, suppresion of miR-21, in respect to their adjacent non-neoplastic tissues, was detected in 24 samples (60 %). In 15 out of these 24 patients (62.5%), we observed that the supression of miR-21 was accompanied by increase of PDCD4 protein levels. Mature miR-21 was overexpressed in 16 out of 40 patients (40%), and in 8 out of these 16 patients (50%) we detected reduced PDCD4 protein levels. Totally, in 23 out of 40 samples (57.5%), the altered miR-21 expression levels correlated with changed PDCD4 protein levels. Conclusion: Our data indicate for the first time that PDCD4 protein expression levels are regulated by miR-21 in non small cell lung cancer tissues. 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 2075.