Abstract 194: Deregulation of miR-222-ABCG2 regulatory module in tongue squamous cell carcinoma contributes to chemoresistance and enhanced metastatic potential

Abstract

Abstract Chemoresistance often associated with other clinical characteristics, such as enhanced metastatic potential. However, the underlying molecular mechanism remains unclear. Our previous studies had revealed that microRNA-222 (miR-222) regulates the cell invasion [Cancer Genomics Proteomics 2009 6:131-138], and plays a role in cell proliferation in tongue squamous cell carcinoma (TSCC) [FEBS Lett. 2010 584(18):4115-20]. The aim of this study is to elucidate the role of miR-222-ABCG2 pathway in the association of cisplatin (cDDP) resistance with enhanced cell migration and invasion ability in TSCC. First, we confirmed the association between cDDP resistance (measured by IC50) and metastatic potential (assessed by migration and invasion assays) using TSCC cell lines and primary cultures from TSCC cases. The siRNA-mediated ABCG2 knockdown led to enhanced cDDP responsiveness, and reduced metastatic potential in TSCC cells. On the contrary, ABCG2 overexpression induced cDDP resistance, and enhanced cell migration and invasion in TSCC cells. Bioinformatics analysis revealed that ABCG2 is a target gene of miR-222, and the direct interaction of miR-222 with ABCG2 mRNA was confirmed by luciferase reporter gene assay. Functional analyses indicated that miR-222 downregulated the expression of ABCG2 gene and enhanced cDDP responsiveness, as well as reduced cell migration and invasion in TSCC cells. Thus, our results confirmed the association between cDDP resistance and enhanced metastatic potential in TSCC. ABCG2 is a direct target gene of miR-222, and deregulation of miR-222-ABCG2 regulatory module in TSCC contributes to both cDDP resistance and enhanced metastatic potential. Citation Format: Anxun Wang, Luodan Zhao, Qianting He, Tingting Zhao, Wei Wang, Xiaofeng Zhou. Deregulation of miR-222-ABCG2 regulatory module in tongue squamous cell carcinoma contributes to chemoresistance and enhanced metastatic potential. [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 194. doi:10.1158/1538-7445.AM2015-194