Abstract 1019: hnRNPA2/B1 upregulates COX-2 expression and tumor growth and predicts poor prognosis in human lung cancers

Abstract

Abstract Constitutive high expression of COX-2 can promote tumor development and has been regarded as a hallmarker for cancers. However, the excise regulation mechanism of COX-2 and its role in lung tumoirgenesis remains unknown. In this study, we discovered and identified hnRNPA2/B1 as a novel regulator of COX-2 promoter in non-small cell lung cancer (NSCLC) cells by a DNA probe-biotin-streptavidin-agarose pulldown and proteomic technique. We showed that hnRNPA2/B1 specifically bound to COX-2 core promoter region, activated COX-2 promoter activity and up-regulated COX-2 expression. Knockdown of hnRNPA2/B1 expression by siRNA significantly suppressed tumor cell growth in NSCLC cell lines in vitro and in a animal model in vivo by inhibiting COX-2 expression. In contrast, overexpression of hnRNPA2/B1 promoted COX-2 expression and tumor cell growth in NSCLC cells. Micro-tissue array and immunohistochemical assay showed that hnRNPA2/B1 expression correlated with COX-2 expression and high expression of hnRNPA2/B1 and COX-2 was associated with worse prognosis in patients with NSCLCs. Mechanistically, hnRNPA2/B1 functions as a regulator of COX-2 to control tumor growth through its interaction with p300, a transcriptional co-activator, in NSCLC cells. Immunoprecipitation and confocal immunofluorescence microscope analysis confirmed the direct interaction of hnRNPA2/B1 with p300 proteins. Overexpression of p300, but not its histon acetyltransferase domain deletion mutation, enhanced the acetylation of hnRNPA2/B1, facilitated the binding of hnRNPA2/B1 to COX-2 promoter, thereby promoted COX-2 expression and tumor cell growth. Therefore, these results indicate that hnRNPA2/B1 acts as an activator to regulate COX-2 expression and tumor growth through the interaction with p300 in NSCLC cells and suggest that the hnRNPA2/B1/COX-2 signaling is a potential therapeutic target for lung cancers. Note: This abstract was not presented at the meeting. Citation Format: Jingshu Wang, Yang Xuan, Wei Guo, Guangwei Du, Wuguo Deng. hnRNPA2/B1 upregulates COX-2 expression and tumor growth and predicts poor prognosis in human lung cancers. [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 1019. doi:10.1158/1538-7445.AM2015-1019