Abstract 1466: QKI, a miRNA-200 target gene, suppresses epithelial-to-mesenchymal transition in oral squamous cell carcinoma cells

Abstract

Abstract Objectives: The microRNA (miR)-200 family plays a major role in specifying the epithelial phenotype by preventing expression of the transcription repressors, ZEB1 and ZEB2, which are well-known regulators of epithelial-to-mesenchymal transition (EMT) in epithelial tumors including oral squamous cell carcinoma (OSCC). Here, we elucidated whether the miR-200 family members control RNA-binding protein quaking (QKI) which is a newly identified tumor suppressor and is regulated during EMT. Methods: We predicted that miR-200a and miR-200b could recognize QKI 3’-UTR by analyzing TargetScan and TCGA head and neck SCC dataset. To further verify the role of miR-200 on QKI in HNSCC, we carried out the functional study in CAL27 and HSC3 cells. Results: Forced expression of miR-200b/a/429 inhibited the expression of ZEB1 and ZEB2, and decreased cell migration in CAL27 and HSC3 cells. QKI expression was also suppressed by miR-200 over-expression, and the 3’-UTR of QKI mRNA was directly targeted by miR-200 in luciferase reporter assays. Interestingly, shRNA-mediated knockdown of QKI led to pronounced EMT and pro-tumor effects in vitro and in vivo studies of OSCC. Conclusion: QKI increases during EMT and is targeted by miR-200; while, it suppresses EMT and tumorigenesis, contradictorily. We suggest that QKI and miR-200 could form a balancing feedback loop maintaining homeostatic responses to EMT-inducing signals. Citation Format: Yoon Ho Ko, Eun Ju Kim, Der Sheng Sun, Hye Sung Won, Young-Ho Ahn. QKI, a miRNA-200 target gene, suppresses epithelial-to-mesenchymal transition in oral squamous cell carcinoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1466. doi:10.1158/1538-7445.AM2017-1466